Scholars@Duke
You-Wen He

You-Wen He

Professor of Integrative Immunobiology
Integrative Immunobiology
he000004@mc.duke.edu
Box 3010 DUMC, 335 Jones Building, Durham, NC 27710
335 Jones Building, 207 Resear, Box 3010 DUMC, Durham, NC 27710
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Selected Publications

Sintilimab (anti-PD-1 antibody) combined with high-dose methotrexate, temozolomide, and rituximab (anti-CD20 antibody) in primary central nervous system lymphoma: a phase 2 study.

Journal Article Signal Transduct Target Ther · September 4, 2024 Primary central nervous system lymphoma (PCNSL) is a rare and frequently fatal lymphoma subtype. The programmed death-1 (PD-1) pathway has emerged as a potential therapeutic target, but the effectiveness of PD-1 antibody sintilimab in combination with immu ... Full text Link to item Cite

Clinical efficacy of CDK4/6 inhibitor plus endocrine therapy in HR-positive/HER2-0 and HER2-low-positive metastatic breast cancer: a secondary analysis of PALOMA-2 and PALOMA-3 trials.

Journal Article EBioMedicine · July 2024 BACKGROUND: Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors in combination with traditional endocrine therapy (ET) are now the recommended first-line treatment for hormone receptor (HR)-positive and HER2-negative metastatic breast cancer (MBC). However, th ... Full text Link to item Cite

Promotion of an Antitumor Immune Program by a Tumor-specific, Complement-activating Antibody.

Journal Article J Immunol · May 15, 2024 Tumor-targeting Abs can be used to initiate an antitumor immune program, which appears essential to achieve a long-term durable clinical response to cancer. We previously identified an anti-complement factor H (CFH) autoantibody associated with patients wi ... Full text Link to item Cite

Impact of HER2-low status for patients with early-stage breast cancer and non-pCR after neoadjuvant chemotherapy: a National Cancer Database Analysis.

Journal Article Breast Cancer Res Treat · February 2024 PURPOSE: To investigate potential differences in pathological complete response (pCR) rates and overall survival (OS) between HER2-low and HER2-zero patients with early-stage hormone receptor (HR)-positive and triple-negative breast cancer (TNBC), in the n ... Full text Open Access Link to item Cite

Complement factor H: a novel innate immune checkpoint in cancer immunotherapy.

Journal Article Front Cell Dev Biol · 2024 The elimination of cancer cells critically depends on the immune system. However, cancers have evolved a variety of defense mechanisms to evade immune monitoring, leading to tumor progression. Complement factor H (CFH), predominately known for its function ... Full text Link to item Cite

Bcl2l1 Deficiency in Osteoblasts Reduces the Trabecular Bone Due to Enhanced Osteoclastogenesis Likely through Osteoblast Apoptosis.

Journal Article Int J Mol Sci · December 10, 2023 Bcl2l1 (Bcl-XL) belongs to the Bcl-2 family, Bcl2 and Bcl2-XL are major anti-apoptotic proteins, and the apoptosis of osteoblasts is a key event for bone homeostasis. As the functions of Bcl2l1 in osteoblasts and bone homeostasis remain unclear, we generat ... Full text Open Access Link to item Cite

Antitumor Immune Mechanisms of the Anti-Complement Factor H Antibody GT103.

Journal Article Mol Cancer Ther · June 1, 2023 Development of novel therapeutic antibodies that not only kill tumor cells but modulate the adaptive immune response has the potential to produce long term anticancer immunity and a durable clinical response. We previously reported the discovery of anti-co ... Full text Link to item Cite

Combination immunotherapy of glioblastoma with dendritic cell cancer vaccines, anti-PD-1 and poly I:C

Journal Article Journal of Pharmaceutical Analysis · June 1, 2023 Glioblastoma (GBM) is a lethal cancer with limited therapeutic options. Dendritic cell (DC)-based cancer vaccines provide a promising approach for GBM treatment. Clinical studies suggest that other immunotherapeutic agents may be combined with DC vaccines ... Full text Cite

Mindin (SPON2) Is Essential for Cutaneous Fibrogenesis in a Mouse Model of Systemic Sclerosis.

Journal Article J Invest Dermatol · May 2023 Systemic sclerosis is a fibrotic disease that initiates in the skin and progresses to internal organs, leading to a poor prognosis. Unraveling the etiology of a chronic, multifactorial disease such as systemic sclerosis has been aided by various animal mod ... Full text Link to item Cite

Snail maintains the stem/progenitor state of skin epithelial cells and carcinomas through the autocrine effect of matricellular protein Mindin.

Journal Article Cell Rep · September 20, 2022 Preservation of a small population of cancer stem cells (CSCs) within a heterogeneous carcinoma serves as a paradigm to understand how select cells in a tissue maintain their undifferentiated status. In both embryogenesis and cancer, Snail has been correla ... Full text Link to item Cite

Editorial: Editor’s Pick 2021: Highlights in Cell Death and Survival

Journal Article Frontiers in Cell and Developmental Biology · May 9, 2022 Full text Cite

Clinically approved combination immunotherapy: Current status, limitations, and future perspective.

Journal Article Curr Res Immunol · 2022 Immune-checkpoint inhibitor-based combination immunotherapy has become a first-line treatment for several major types of cancer including hepatocellular carcinoma (HCC), renal cell carcinoma, lung cancer, cervical cancer, and gastric cancer. Combination im ... Full text Open Access Link to item Cite

Class I PI3K Provide Lipid Substrate in T Cell Autophagy Through Linked Activity of Inositol Phosphatases

Journal Article Frontiers in Cell and Developmental Biology · August 12, 2021 Featured Publication Autophagy, a highly conserved intracellular process, has been identified as a novel mechanism regulating T lymphocyte homeostasis. Herein, we demonstrate that both starvation- and T cell receptor-mediated autophagy induction requires class I phosphatidylin ... Full text Cite

Antiapoptotic Bcl-2 family proteins BCL-xL and MCL-1 integrate neural progenitor survival and proliferation during postnatal cerebellar neurogenesis.

Journal Article Cell Death Differ · May 2021 Featured Publication The tendency of brain cells to undergo apoptosis in response to exogenous events varies across neural development, with apoptotic threshold dependent on proliferation state. Proliferative neural progenitors show a low threshold for apoptosis, while termina ... Full text Link to item Cite

MicroRNA-29 is an essential regulator of brain maturation through regulation of CH methylation.

Journal Article Cell Rep · April 6, 2021 Featured Publication Although embryonic brain development and neurodegeneration have received considerable attention, the events that govern postnatal brain maturation are less understood. Here, we identify the miR-29 family to be strikingly induced during the late stages of b ... Full text Open Access Link to item Cite

Conversion of effector CD4+ T cells to a CD8+ MHC II-recognizing lineage.

Journal Article Cell Mol Immunol · January 2021 CD4+ and CD8+ T cells are dichotomous lineages in adaptive immunity. While conventionally viewed as distinct fates that are fixed after thymic development, accumulating evidence indicates that these two populations can exhibit significant lineage plasticit ... Full text Link to item Cite

A Potential Role of Interleukin 10 in COVID-19 Pathogenesis.

Journal Article Trends Immunol · January 2021 Featured Publication A unique feature of the cytokine storm in coronavirus disease 2019 (COVID-19) is the dramatic elevation of interleukin 10 (IL-10). This was thought to be a negative feedback mechanism to suppress inflammation. However, several lines of clinical evidence su ... Full text Link to item Cite

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

Journal Article Autophagy · January 2021 In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been ... Full text Link to item Cite

Sintilimab (anti-PD-1 antibody) combined with high-dose methotrexate, temozolomide, and rituximab (anti-CD20 antibody) in primary central nervous system lymphoma: a phase 2 study.

Journal Article Signal Transduct Target Ther · September 4, 2024 Primary central nervous system lymphoma (PCNSL) is a rare and frequently fatal lymphoma subtype. The programmed death-1 (PD-1) pathway has emerged as a potential therapeutic target, but the effectiveness of PD-1 antibody sintilimab in combination with immu ... Full text Link to item Cite

Clinical efficacy of CDK4/6 inhibitor plus endocrine therapy in HR-positive/HER2-0 and HER2-low-positive metastatic breast cancer: a secondary analysis of PALOMA-2 and PALOMA-3 trials.

Journal Article EBioMedicine · July 2024 BACKGROUND: Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors in combination with traditional endocrine therapy (ET) are now the recommended first-line treatment for hormone receptor (HR)-positive and HER2-negative metastatic breast cancer (MBC). However, th ... Full text Link to item Cite

Promotion of an Antitumor Immune Program by a Tumor-specific, Complement-activating Antibody.

Journal Article J Immunol · May 15, 2024 Tumor-targeting Abs can be used to initiate an antitumor immune program, which appears essential to achieve a long-term durable clinical response to cancer. We previously identified an anti-complement factor H (CFH) autoantibody associated with patients wi ... Full text Link to item Cite

Impact of HER2-low status for patients with early-stage breast cancer and non-pCR after neoadjuvant chemotherapy: a National Cancer Database Analysis.

Journal Article Breast Cancer Res Treat · February 2024 PURPOSE: To investigate potential differences in pathological complete response (pCR) rates and overall survival (OS) between HER2-low and HER2-zero patients with early-stage hormone receptor (HR)-positive and triple-negative breast cancer (TNBC), in the n ... Full text Open Access Link to item Cite

Complement factor H: a novel innate immune checkpoint in cancer immunotherapy.

Journal Article Front Cell Dev Biol · 2024 The elimination of cancer cells critically depends on the immune system. However, cancers have evolved a variety of defense mechanisms to evade immune monitoring, leading to tumor progression. Complement factor H (CFH), predominately known for its function ... Full text Link to item Cite

Bcl2l1 Deficiency in Osteoblasts Reduces the Trabecular Bone Due to Enhanced Osteoclastogenesis Likely through Osteoblast Apoptosis.

Journal Article Int J Mol Sci · December 10, 2023 Bcl2l1 (Bcl-XL) belongs to the Bcl-2 family, Bcl2 and Bcl2-XL are major anti-apoptotic proteins, and the apoptosis of osteoblasts is a key event for bone homeostasis. As the functions of Bcl2l1 in osteoblasts and bone homeostasis remain unclear, we generat ... Full text Open Access Link to item Cite

Antitumor Immune Mechanisms of the Anti-Complement Factor H Antibody GT103.

Journal Article Mol Cancer Ther · June 1, 2023 Development of novel therapeutic antibodies that not only kill tumor cells but modulate the adaptive immune response has the potential to produce long term anticancer immunity and a durable clinical response. We previously reported the discovery of anti-co ... Full text Link to item Cite

Combination immunotherapy of glioblastoma with dendritic cell cancer vaccines, anti-PD-1 and poly I:C

Journal Article Journal of Pharmaceutical Analysis · June 1, 2023 Glioblastoma (GBM) is a lethal cancer with limited therapeutic options. Dendritic cell (DC)-based cancer vaccines provide a promising approach for GBM treatment. Clinical studies suggest that other immunotherapeutic agents may be combined with DC vaccines ... Full text Cite

Mindin (SPON2) Is Essential for Cutaneous Fibrogenesis in a Mouse Model of Systemic Sclerosis.

Journal Article J Invest Dermatol · May 2023 Systemic sclerosis is a fibrotic disease that initiates in the skin and progresses to internal organs, leading to a poor prognosis. Unraveling the etiology of a chronic, multifactorial disease such as systemic sclerosis has been aided by various animal mod ... Full text Link to item Cite

Snail maintains the stem/progenitor state of skin epithelial cells and carcinomas through the autocrine effect of matricellular protein Mindin.

Journal Article Cell Rep · September 20, 2022 Preservation of a small population of cancer stem cells (CSCs) within a heterogeneous carcinoma serves as a paradigm to understand how select cells in a tissue maintain their undifferentiated status. In both embryogenesis and cancer, Snail has been correla ... Full text Link to item Cite

Editorial: Editor’s Pick 2021: Highlights in Cell Death and Survival

Journal Article Frontiers in Cell and Developmental Biology · May 9, 2022 Full text Cite

Clinically approved combination immunotherapy: Current status, limitations, and future perspective.

Journal Article Curr Res Immunol · 2022 Immune-checkpoint inhibitor-based combination immunotherapy has become a first-line treatment for several major types of cancer including hepatocellular carcinoma (HCC), renal cell carcinoma, lung cancer, cervical cancer, and gastric cancer. Combination im ... Full text Open Access Link to item Cite

Class I PI3K Provide Lipid Substrate in T Cell Autophagy Through Linked Activity of Inositol Phosphatases

Journal Article Frontiers in Cell and Developmental Biology · August 12, 2021 Featured Publication Autophagy, a highly conserved intracellular process, has been identified as a novel mechanism regulating T lymphocyte homeostasis. Herein, we demonstrate that both starvation- and T cell receptor-mediated autophagy induction requires class I phosphatidylin ... Full text Cite

Antiapoptotic Bcl-2 family proteins BCL-xL and MCL-1 integrate neural progenitor survival and proliferation during postnatal cerebellar neurogenesis.

Journal Article Cell Death Differ · May 2021 Featured Publication The tendency of brain cells to undergo apoptosis in response to exogenous events varies across neural development, with apoptotic threshold dependent on proliferation state. Proliferative neural progenitors show a low threshold for apoptosis, while termina ... Full text Link to item Cite

MicroRNA-29 is an essential regulator of brain maturation through regulation of CH methylation.

Journal Article Cell Rep · April 6, 2021 Featured Publication Although embryonic brain development and neurodegeneration have received considerable attention, the events that govern postnatal brain maturation are less understood. Here, we identify the miR-29 family to be strikingly induced during the late stages of b ... Full text Open Access Link to item Cite

Conversion of effector CD4+ T cells to a CD8+ MHC II-recognizing lineage.

Journal Article Cell Mol Immunol · January 2021 CD4+ and CD8+ T cells are dichotomous lineages in adaptive immunity. While conventionally viewed as distinct fates that are fixed after thymic development, accumulating evidence indicates that these two populations can exhibit significant lineage plasticit ... Full text Link to item Cite

A Potential Role of Interleukin 10 in COVID-19 Pathogenesis.

Journal Article Trends Immunol · January 2021 Featured Publication A unique feature of the cytokine storm in coronavirus disease 2019 (COVID-19) is the dramatic elevation of interleukin 10 (IL-10). This was thought to be a negative feedback mechanism to suppress inflammation. However, several lines of clinical evidence su ... Full text Link to item Cite

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

Journal Article Autophagy · January 2021 In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been ... Full text Link to item Cite

Antibody response and therapy in COVID-19 patients: what can be learned for vaccine development?

Journal Article Sci China Life Sci · December 2020 Featured Publication The newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected millions of people and caused tremendous morbidity and mortality worldwide. Effective treatment for coronavirus disease 2019 (COVID-19) due to SARS-CoV-2 infection ... Full text Link to item Cite

Tumor-associated antigen-based personalized dendritic cell vaccine in solid tumor patients.

Journal Article Cancer Immunol Immunother · July 2020 Featured Publication Tumor-associated antigens (TAAs) have been tested in various clinical trials in cancer treatment but the patterns of specific T cell response to personalized TAA immunization remains to be fully understood. We report antigen-specific T cell responses in pa ... Full text Link to item Cite

Enhanced Human T Lymphocyte Antigen Priming by Cytokine-Matured Dendritic Cells Overexpressing Bcl-2 and IL-12.

Journal Article Front Cell Dev Biol · 2020 Featured Publication Dendritic cell (DC)-based vaccination is a promising immunotherapeutic strategy for cancer. However, clinical trials have shown only limited efficacy, suggesting the need to optimize protocols for human DC vaccine preparation. In this study, we systemicall ... Full text Link to item Cite

Preventing Mortality in COVID-19 Patients: Which Cytokine to Target in a Raging Storm?

Journal Article Front Cell Dev Biol · 2020 Featured Publication Coronavirus disease 2019 (COVID-19) from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has resulted in tremendous morbidity and mortality worldwide. A major underlying cause of COVID-19 mortality is a hyperinflammatory cytokine sto ... Full text Link to item Cite

Low human and murine Mcl-1 expression leads to a pro-apoptotic plaque phenotype enriched in giant-cells.

Journal Article Sci Rep · October 10, 2019 The anti-apoptotic protein myeloid cell leukemia 1 (Mcl-1) plays an important role in survival and differentiation of leukocytes, more specifically of neutrophils. Here, we investigated the impact of myeloid Mcl-1 deletion in atherosclerosis. Western type ... Full text Link to item Cite

Modulation of NKG2D, KIR2DL and Cytokine Production by Pleurotus ostreatus Glucan Enhances Natural Killer Cell Cytotoxicity Toward Cancer Cells

Journal Article Frontiers in Cell and Developmental Biology · August 13, 2019 Medicinal mushrooms have been used for centuries against cancer and infectious diseases. These positive biological effects of mushrooms are due in part to the indirect action of stimulating immune cells. The objective of the current study is to investigate ... Full text Open Access Cite

Molecular Docking and Molecular Dynamics (MD) Simulation of Human Anti-Complement Factor H (CFH) Antibody Ab42 and CFH Polypeptide.

Journal Article Int J Mol Sci · May 25, 2019 An understanding of the interaction between the antibody and its targeted antigen and knowing of the epitopes are critical for the development of monoclonal antibody drugs. Complement factor H (CFH) is implied to play a role in tumor growth and metastasis. ... Full text Link to item Cite

The Complement Receptors C3aR and C5aR Are a New Class of Immune Checkpoint Receptor in Cancer Immunotherapy.

Journal Article Front Immunol · 2019 Cancer immunotherapy has made remarkable clinical advances in recent years. Antibodies targeting the immune checkpoint receptors PD-1 and CTLA-4 and adoptive cell therapy (ACT) based on ex vivo expanded peripheral CTLs, tumor infiltrating lymphocytes (TILs ... Full text Open Access Link to item Cite

A Multi-Element Expression Score Is A Prognostic Factor In Glioblastoma Multiforme.

Journal Article Cancer Manag Res · 2019 Featured Publication PURPOSE: Glioblastoma multiforme (GBM) is a highly malignant tumor of the central nervous system. Although primary GBM patients receive extensive therapies, tumors may recur within months, and there is no objective and scientific method to predict prognosi ... Full text Link to item Cite

Myeloid-Specific Deletion of Mcl-1 Yields Severely Neutropenic Mice That Survive and Breed in Homozygous Form.

Journal Article J Immunol · December 15, 2018 Featured Publication Mouse strains with specific deficiency of given hematopoietic lineages provide invaluable tools for understanding blood cell function in health and disease. Whereas neutrophils are dominant leukocytes in humans and mice, there are no widely useful genetic ... Full text Link to item Cite

Crosstalk in competing endogenous RNA networks reveals new circular RNAs involved in the pathogenesis of early HIV infection.

Journal Article J Transl Med · November 29, 2018 BACKGROUND: The events in early HIV infection (EHI) are important determinants of disease severity and progression rate to AIDS, but the mechanisms of pathogenesis in EHI have not been fully understood. Circular RNAs (circRNAs) have been verified as "micro ... Full text Link to item Cite

The Role of Macroautophagy in T Cells

Chapter · January 1, 2018 Featured Publication The highly conserved self-digestion pathway macroautophagy (hereafter referred to as autophagy) maintains the homeostasis of organelles, degrades long-lived proteins, and recycles amino acids under starvation conditions. Autophagy related molecules are exp ... Full text Cite

The Mcl-1 Delta Myelo mice are highly susceptible to microbial infections

Conference EUROPEAN JOURNAL OF CLINICAL INVESTIGATION · May 1, 2017 Featured Publication Link to item Cite

Interleukin-10: An Immune-Activating Cytokine in Cancer Immunotherapy.

Journal Article J Clin Oncol · October 10, 2016 Featured Publication Full text Link to item Cite

Lung inflammation stalls Th17-cell migration en route to the central nervous system during the development of experimental autoimmune encephalomyelitis.

Journal Article Int Immunol · September 2016 Recruiting pathogenic T cells to the central nervous system (CNS) is a critical step during the development of experimental autoimmune encephalomyelitis (EAE). Here, we report that the absence of autophagy and microtubule-associated protein 1A/1B-light cha ... Full text Link to item Cite

Autocrine Complement Inhibits IL10-Dependent T-cell-Mediated Antitumor Immunity to Promote Tumor Progression.

Journal Article Cancer Discov · September 2016 Featured Publication UNLABELLED: In contrast to its inhibitory effects on many cells, IL10 activates CD8(+) tumor-infiltrating lymphocytes (TIL) and enhances their antitumor activity. However, CD8(+) TILs do not routinely express IL10, as autocrine complement C3 inhibits IL10 ... Full text Link to item Cite

Bcl-xL is an oncogenic driver in colorectal cancer.

Journal Article Cell Death Dis · August 18, 2016 Featured Publication Colorectal cancer (CRC) is the second most common malignant neoplasia in women and men worldwide. The B-cell lymphoma 2 (Bcl-2) protein family is mainly known for its pivotal role in the regulation of the mitochondrial death pathway. Anti-apoptotic Bcl-2 p ... Full text Link to item Cite

Cellular FLIP Inhibits Myeloid Cell Activation by Suppressing Selective Innate Signaling.

Journal Article J Immunol · September 15, 2015 Featured Publication Cellular FLIP (c-FLIP) specifically inhibits caspase-8 and suppresses death receptor-induced apoptosis. c-FLIP has also been reported to transmit activation signals. In this study, we report a novel function of c-FLIP involving inhibition of myeloid cell a ... Full text Link to item Cite

Regulation of T cell function by microRNA-720.

Journal Article Sci Rep · July 22, 2015 Featured Publication Chronic hepatitis B virus (HBV) infection is a major global health burden. Functional exhaustion and numerical reduction of HBV-specific cytotoxic T lymphocytes (CTLs) in the liver and peripheral blood limit anti-HBV CTL activity in patients with chronic H ... Full text Link to item Cite

The lung is protected from spontaneous inflammation by autophagy in myeloid cells.

Journal Article J Immunol · June 1, 2015 Featured Publication The lung is constantly exposed to the outer environment; thus, it must maintain a state of immune ignorance or tolerance not to overrespond to harmless environmental stimuli. How cells in the lung control immune responses under nonpathogenic condition is n ... Full text Link to item Cite

Acute organ failure following the loss of anti-apoptotic cellular FLICE-inhibitory protein involves activation of innate immune receptors.

Journal Article Cell Death Differ · May 2015 Featured Publication Apoptosis signaling is involved in both physiological tissue homeostasis and acute and chronic diseases. The role of regulatory apoptosis signaling molecules and their organ-specific functions are less defined. Therefore, we investigated the loss of the an ... Full text Link to item Cite

Characterization of a novel neutrophil-deficient mouse strain

Journal Article EUROPEAN JOURNAL OF CLINICAL INVESTIGATION · May 1, 2015 Featured Publication Link to item Cite

c-FLIP protects T lymphocytes from apoptosis in the intrinsic pathway.

Journal Article J Immunol · April 1, 2015 Featured Publication Apoptosis can be induced by either death receptors on the plasma membrane (extrinsic pathway) or the damage of the genome and/or cellular organelles (intrinsic pathway). Previous studies suggest that cellular caspase 8 (FLICE)-like inhibitory protein (c-FL ... Full text Link to item Cite

Involvement of BCL-XL in regulation of mast cell survival

Conference EXPERIMENTAL DERMATOLOGY · March 1, 2015 Link to item Cite

Autophagy enhances NFκB activity in specific tissue macrophages by sequestering A20 to boost antifungal immunity.

Journal Article Nat Commun · January 22, 2015 Immune responses must be well restrained in a steady state to avoid excessive inflammation. However, such restraints are quickly removed to exert antimicrobial responses. Here we report a role of autophagy in an early host antifungal response by enhancing ... Full text Open Access Link to item Cite

Autophagy regulates T lymphocyte proliferation through selective degradation of the cell-cycle inhibitor CDKN1B/p27Kip1.

Journal Article Autophagy · 2015 Featured Publication The highly conserved cellular degradation pathway, macroautophagy, regulates the homeostasis of organelles and promotes the survival of T lymphocytes. Previous results indicate that Atg3-, Atg5-, or Pik3c3/Vps34-deficient T cells cannot proliferate efficie ... Full text Link to item Cite

Applications of RNA interference high-throughput screening technology in cancer biology and virology.

Journal Article Protein Cell · November 2014 Featured Publication RNA interference (RNAi) is an ancient intra-cellular mechanism that regulates gene expression and cell function. Large-scale gene silencing using RNAi high-throughput screening (HTS) has opened an exciting frontier to systematically study gene function in ... Full text Link to item Cite

Regulation of T cell proliferation by JMJD6 and PDGF-BB during chronic hepatitis B infection.

Journal Article Sci Rep · September 15, 2014 Featured Publication T cell functional exhaustion during chronic hepatitis B virus (HBV) infection may contribute to the failed viral clearance; however, the underlying molecular mechanisms remain largely unknown. Here we demonstrate that jumonji domain-containing protein 6 (J ... Full text Link to item Cite

Participation of c-FLIP in NLRP3 and AIM2 inflammasome activation.

Journal Article Cell Death Differ · March 2014 Featured Publication Cellular FLICE-inhibitory protein (c-FLIP) is an inhibitor of caspase-8 and is required for macrophage survival. Recent studies have revealed a selective role of caspase-8 in noncanonical IL-1β production that is independent of caspase-1 or inflammasome. H ... Full text Link to item Cite

The c-FLIPL cleavage product p43FLIP promotes activation of extracellular signal-regulated kinase (ERK), nuclear factor κB (NF-κB), and caspase-8 and T cell survival.

Journal Article J Biol Chem · January 10, 2014 Featured Publication Caspase-8 is now appreciated to govern both apoptosis following death receptor ligation and cell survival and growth via inhibition of the Ripoptosome. Cells must therefore carefully regulate the high level of caspase-8 activity during apoptosis versus the ... Full text Link to item Cite

c-FLIP protects eosinophils from TNF-α-mediated cell death in vivo.

Journal Article PLoS One · 2014 Featured Publication Understanding the signals that regulate eosinophil survival and death is critical to developing new treatments for asthma, atopy, and gastrointestinal disease. Previous studies suggest that TNF-α stimulation protects eosinophils from apoptosis, and this TN ... Full text Link to item Cite

Plasma microRNA signature as a noninvasive biomarker for acute graft-versus-host disease.

Journal Article Blood · November 7, 2013 Featured Publication Acute graft-versus-host disease (aGVHD) is the leading cause of morbidity and mortality after allogeneic hematopoietic cell transplantation (HCT). Approximately 35% to 50% of HCT recipients develop aGVHD; however, there are no validated diagnostic and pred ... Full text Link to item Cite

cFLIP regulates skin homeostasis and protects against TNF-induced keratinocyte apoptosis.

Journal Article Cell Rep · October 31, 2013 Featured Publication FADD, caspase-8, and cFLIP regulate the outcome of cell death signaling. Mice that constitutively lack these molecules die at an early embryonic age, whereas tissue-specific constitutive deletion of FADD or caspase-8 results in inflammatory skin disease ca ... Full text Link to item Cite

Autophagy, a novel pathway to regulate calcium mobilization in T lymphocytes

Journal Article Frontiers in Immunology · September 16, 2013 Featured Publication The T lymphocyte response initiates with the recognition of MHC/peptides on antigen presenting cells by the T cell receptor (TCR). After the TCR engagement, the proximal signaling pathways are activated for downstream cellular events. Among these pathways, ... Full text Cite

Transcriptomic analysis of peripheral blood mononuclear cells in rapid progressors in early HIV infection identifies a signature closely correlated with disease progression.

Journal Article Clin Chem · August 2013 Featured Publication BACKGROUND: A substantial percentage (10%-15%) of HIV-infected individuals experience a sharp decline in CD4(+) T-cell counts and progress to AIDS quickly after primary infection. Identification of biomarkers distinguishing rapid progressors (RPs) vs chron ... Full text Link to item Cite

Diabetic liver injury from streptozotocin is regulated through the caspase-8 homolog cFLIP involving activation of JNK2 and intrahepatic immunocompetent cells.

Journal Article Cell Death Dis · July 4, 2013 The endemic occurrence of obesity and the associated risk factors that constitute the metabolic syndrome have been predicted to lead to a dramatic increase in chronic liver disease. Non-alcoholic steatohepatitis (NASH) has become the most frequent liver di ... Full text Link to item Cite

CFLAR/c-FLIPL: a star in the autophagy, apoptosis and necroptosis alliance.

Journal Article Autophagy · May 2013 Featured Publication Necroptosis, a caspase-independent, receptor (TNFRSF)-interacting serine-threonine kinase 1 (RIPK1)/RIPK3-dependent necrotic cell death, occurs in cells when apoptosis is blocked. A high level of macroautophagy (herein referred to as autophagy) is usually ... Full text Link to item Cite

A role for c-FLIP(L) in the regulation of apoptosis, autophagy, and necroptosis in T lymphocytes.

Journal Article Cell Death Differ · February 2013 Featured Publication Caspase 8 plays a dual role in the survival of T lymphocytes. Although active caspase 8 mediates apoptosis upon death receptor signaling, the loss of caspase 8 activity leads to receptor-interacting protein (RIP)-1/RIP-3-dependent necrotic cell death (necr ... Full text Link to item Cite

Transfer of CD8+ T cell memory using Bcl-2 as a marker.

Journal Article J Immunol · February 1, 2013 Featured Publication The processes that regulate T cell memory generation are important for therapeutic design and the immune response to disease. However, what allows a subset of effector T cells to survive the contraction period to become memory cells is incompletely underst ... Full text Link to item Cite

Cellular FLICE-like inhibitory protein secures intestinal epithelial cell survival and immune homeostasis by regulating caspase-8

Journal Article Gastroenterology · January 1, 2013 Background & Aims The intestinal epithelium generates a barrier that protects mammals from potentially harmful intestinal contents, such as pathogenic bacteria. Dysregulation of epithelial cell death has been implicated in barrier dysfunction and in the pa ... Full text Cite

A novel antibody humanization method based on epitopes scanning and molecular dynamics simulation.

Journal Article PLoS One · 2013 1-17-2 is a rat anti-human DEC-205 monoclonal antibody that induces internalization and delivers antigen to dendritic cells (DCs). The potentially clinical application of this antibody is limited by its murine origin. Traditional humanization method such a ... Full text Link to item Cite

Role of the Autophagy Gene Atg5 in T Lymphocyte Survival and Proliferation

Journal Article · January 1, 2013 Featured Publication Macroautophagy (referred to as autophagy) is a highly conserved intracellular process that involves sequestration of cytoplasmic contents by intracellular double-membrane vacuoles. In the adaptive immune system, autophagy is essential for antigen presentat ... Full text Cite

T lymphocytes from chronic HCV-infected patients are primed for activation-induced apoptosis and express unique pro-apoptotic gene signature.

Journal Article PLoS One · 2013 Featured Publication Although extensive studies have demonstrated the functional impairment of antigen-specific CD4(+) and CD8(+) T-cells during chronic hepatitis C virus (HCV) infection, the functional status of global CD4(+) and CD8(+) T-cells remains unclear. In this report ... Full text Link to item Cite

c-FLIP maintains tissue homeostasis by preventing apoptosis and programmed necrosis.

Journal Article Sci Signal · December 18, 2012 Featured Publication As a catalytically inactive homolog of caspase-8, a proapoptotic initiator caspase, c-FLIP blocks apoptosis by binding to and inhibiting caspase-8. The transcription factor nuclear factor κB (NF-κB) plays a pivotal role in maintaining the homeostasis of th ... Full text Link to item Cite

The diverse roles of autophagy in immunity

Journal Article · December 1, 2012 Autophagy is a highly conserved process in all eukaryotic organisms that has been adapted for a multitude of divergent functions. The mammalian immune system is no exception, with various hematopoietic cells utilizing this intracellular remodeling process ... Cite

The contribution of autophagy to lymphocyte survival and homeostasis.

Journal Article Immunol Rev · September 2012 Featured Publication Over the life span of a T lymphocyte, from thymic development to death, it is subjected to a variety of stresses and stimuli. Upon receipt of each stress or stimulus, a potentially life-changing fate decision must be made, namely, whether to commit to a fo ... Full text Link to item Cite

Editorial: TRPV1: how thymocytes sense stress and respond with autophagy.

Journal Article J Leukoc Biol · September 2012 Featured Publication Discussion on discovery of the roles of TRPV1 in thymocyte autophagy, and its relevance. ... Full text Link to item Cite

Increased hepatic fibrosis and JNK2-dependent liver injury in mice exhibiting hepatocyte-specific deletion of cFLIP.

Journal Article Am J Physiol Gastrointest Liver Physiol · August 15, 2012 Chronic liver disease promotes hepatocellular injury involving apoptosis and triggers compensatory regeneration that leads to the activation of quiescent stellate cells in the liver. The deposition of extracellular matrix from activated myofibroblasts prom ... Full text Link to item Cite

Autophagic activity dictates the cellular response to oncogenic RAS.

Journal Article Proc Natl Acad Sci U S A · August 14, 2012 Featured Publication RAS is frequently mutated in human cancers and has opposing effects on autophagy and tumorigenesis. Identifying determinants of the cellular responses to RAS is therefore vital in cancer research. Here, we show that autophagic activity dictates the cellula ... Full text Link to item Cite

Disruption of mindin exacerbates cardiac hypertrophy and fibrosis.

Journal Article J Mol Med (Berl) · August 2012 Cardiac hypertrophy is a response of the myocardium to increased workload and is characterised by an increase of myocardial mass and an accumulation of extracellular matrix (ECM). As an ECM protein, an integrin ligand, and an angiogenesis inhibitor, all of ... Full text Link to item Cite

Selective autophagy of the adaptor protein Bcl10 modulates T cell receptor activation of NF-κB.

Journal Article Immunity · June 29, 2012 Featured Publication The adaptor protein Bcl10 is a critically important mediator of T cell receptor (TCR)-to-NF-κB signaling. Bcl10 degradation is a poorly understood biological phenomenon suggested to reduce TCR activation of NF-κB. Here we have shown that TCR engagement tri ... Full text Link to item Cite

The role of death effector domain-containing proteins in acute oxidative cell injury in hepatocytes.

Journal Article Free Radic Biol Med · May 1, 2012 Apoptosis is a mechanism that regulates hepatic tissue homeostasis and contributes to both acute and chronic injury in liver disease. The apoptotic signaling cascade involves activation of the death-inducing signaling complex (DISC) and subsequent recruitm ... Full text Link to item Cite

Guidelines for the use and interpretation of assays for monitoring autophagy.

Journal Article Autophagy · April 2012 In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have ... Full text Link to item Cite

Macroautophagy in T lymphocyte development and function.

Journal Article Front Immunol · 2012 Featured Publication Macroautophagy (referred to as autophagy) is a fundamental intracellular process characterized by the sequestration of cytoplasmic compartments through double-membrane vesicles, termed autophagosomes. Recent studies have established important roles of auto ... Full text Link to item Cite

Downregulation of the AU-rich RNA-binding protein ZFP36 in chronic HBV patients: implications for anti-inflammatory therapy.

Journal Article PLoS One · 2012 Featured Publication Inflammation caused by chronic hepatitis B virus (HBV) infection is associated with the development of cirrhosis and hepatocellular carcinoma; however, the mechanisms by which HBV infection induces inflammation and inflammatory cytokine production remain l ... Full text Link to item Cite

Structure-based high-throughput epitope analysis of hexon proteins in B and C species human adenoviruses (HAdVs).

Journal Article PLoS One · 2012 Human adenoviruses (HAdVs) are the etiologic agent of many human infectious diseases. The existence of at least 54 different serotypes of HAdVs has resulted in difficulties in clinical diagnosis. Acute respiratory tract disease (ARD) caused by some serotyp ... Full text Link to item Cite

The prolyl isomerase Pin1 modulates development of CD8+ cDC in mice.

Journal Article PLoS One · 2012 BACKGROUND: Pin1 has previously been described to regulate cells that participate in both innate and adaptive immunity. Thus far, however, no role for Pin1 has been described in modulating conventional dendritic cells, innate antigen presenting cells that ... Full text Link to item Cite

The crosstalk between autophagy and apoptosis: where does this lead?

Journal Article Protein Cell · January 2012 Featured Publication Recent advances in the understanding of the molecular processes contributing to autophagy have provided insight into the relationship between autophagy and apoptosis. In contrast to the concept of "autophagic cell death," accumulating evidence suggests tha ... Full text Link to item Cite

Endocytosis by target cells: An essential means for perforin-and granzyme-mediated killing

Journal Article Cellular and Molecular Immunology · January 1, 2012 Full text Cite

IL-15 regulates homeostasis and terminal maturation of NKT cells.

Journal Article J Immunol · December 15, 2011 Semi-invariant NKT cells are thymus-derived innate-like lymphocytes that modulate microbial and tumor immunity as well as autoimmune diseases. These immunoregulatory properties of NKT cells are acquired during their development. Much has been learned regar ... Full text Link to item Cite

Ablation of c-FLIP in hepatocytes enhances death-receptor mediated apoptosis and toxic liver injury in vivo.

Journal Article J Hepatol · December 2011 Featured Publication BACKGROUND & AIMS: Apoptosis is crucially involved in acute and chronic liver injury, including viral, cholestatic, toxic, and metabolic liver disease. Additionally, dysregulation of apoptosis signaling pathways has been implicated in hepatocarcinogenesis. ... Full text Link to item Cite

The class III kinase Vps34 promotes T lymphocyte survival through regulating IL-7Rα surface expression.

Journal Article J Immunol · November 15, 2011 Featured Publication IL-7Rα-mediated signals are essential for naive T lymphocyte survival. Recent studies show that IL-7Rα is internalized and either recycled to cell surface or degraded. However, how the intracellular process of IL-7Rα trafficking is regulated is unclear. In ... Full text Link to item Cite

Regulation of T-cell survival and mitochondrial homeostasis by TSC1.

Journal Article Eur J Immunol · November 2011 The mammalian target of rapamycin (mTOR) is a key regulator of cell growth and metabolism. It associates with multiple proteins and forms two distinct signaling complexes, mTORC1 and mTORC2. Accumulating evidence has revealed critical roles for intact mTOR ... Full text Link to item Cite

Cytokine-dependent and cytokine-independent roles for Mcl-1: genetic evidence for multiple mechanisms by which Mcl-1 promotes survival in primary T lymphocytes.

Journal Article Cell Death Dis · October 6, 2011 Featured Publication Myeloid cell leukemia sequence-1 (Mcl-1) is a critical anti-apoptotic factor in T lymphocytes. However, in spite of the many pro-apoptotic proteins with proposed binding to Mcl-1, the specific interactions by which Mcl-1 regulates primary T-cell survival u ... Full text Link to item Cite

The role of the extracellular matrix protein mindin in airway response to environmental airways injury.

Journal Article Environ Health Perspect · October 2011 BACKGROUND: Our previous work demonstrated that the extracellular matrix protein mindin contributes to allergic airways disease. However, the role of mindin in nonallergic airways disease has not previously been explored. OBJECTIVES: We hypothesized that m ... Full text Link to item Cite

Cardiac-specific mindin overexpression attenuates cardiac hypertrophy via blocking AKT/GSK3β and TGF-β1-Smad signalling.

Journal Article Cardiovasc Res · October 1, 2011 AIMS: Mindin is a secreted extracellular matrix protein, an integrin ligand, and an angiogenesis inhibitor, other examples of which are all key players in the progression of cardiac hypertrophy. However, its function during cardiac hypertrophy remains uncl ... Full text Link to item Cite

Temporal regulation of intracellular organelle homeostasis in T lymphocytes by autophagy.

Journal Article J Immunol · May 1, 2011 Featured Publication The highly conserved self-degradation pathway known as autophagy plays important roles in regulating T lymphocyte homeostasis. Recently, we found that T lymphocytes lacking the autophagy-related gene Atg5 or Atg7 have defective survival and contain expande ... Full text Link to item Cite

Autophagy is essential to suppress cell stress and to allow BCR-Abl-mediated leukemogenesis.

Journal Article Oncogene · April 21, 2011 Featured Publication Hematopoietic cells normally require cell extrinsic signals to maintain metabolism and survival. In contrast, cancer cells can express constitutively active oncogenic kinases such as BCR-Abl that promote these processes independent of extrinsic growth fact ... Full text Link to item Cite

Apoptosis and autophagy in the regulation of T lymphocyte function.

Journal Article Immunol Res · April 2011 Featured Publication During the development and normal function of T lymphocytes, the cells are subject to several checkpoints at which they must "decide" to live or die. At these critical times and during homeostasis, the molecules that regulate the classical apoptotic pathwa ... Full text Link to item Cite

Autophagy regulates endoplasmic reticulum homeostasis and calcium mobilization in T lymphocytes.

Journal Article J Immunol · February 1, 2011 Featured Publication Macroautophagy (hereafter referred to as autophagy) is an evolutionarily conserved intracellular bulk degradation pathway that plays critical roles in eliminating intracellular pathogens, presenting endogenous Ags, and regulating T lymphocyte survival and ... Full text Link to item Cite

Regulation of steady-state neutrophil homeostasis by macrophages.

Journal Article Blood · January 13, 2011 Featured Publication The timely clearance of apoptotic neutrophils from inflammation sites is an important function of macrophages; however, the role of macrophages in maintaining neutrophil homeostasis under steady-state conditions is less well understood. By conditionally de ... Full text Link to item Cite

Mcl-1 promotes survival of thymocytes by inhibition of Bak in a pathway separate from Bcl-2.

Journal Article Cell Death Differ · June 2010 Featured Publication The antiapoptotic proteins Mcl-1 and Bcl-2 have been shown to be critical in T-cell development and homeostasis, but the precise mechanism by which these proteins function in T cells and other cells of the body is unclear. Potential mechanisms have allowed ... Full text Link to item Cite

Deletion of PIK3C3/Vps34 in sensory neurons causes rapid neurodegeneration by disrupting the endosomal but not the autophagic pathway.

Journal Article Proc Natl Acad Sci U S A · May 18, 2010 The lipid kinase PIK3C3 (also called Vps34) regulates both the endosomal and autophagic pathways. However, the effect of inactivating PIK3C3 on neuronal endosomal versus autophagic processes in vivo has not been studied. We generated mice in which Pik3c3 w ... Full text Link to item Cite

Roles of autophagy in lymphocytes: reflections and directions.

Journal Article Cell Mol Immunol · March 2010 Recent studies have revealed that autophagy, a fundamental intracellular process, plays many different roles in lymphocyte development and function. Autophagy regulates naive T-lymphocyte homeostasis, specifically by regulating mitochondrial quality and tu ... Full text Link to item Cite

A single amino acid defines cross-species reactivity of tree shrew (Tupaia belangeri) CD1d to human invariant natural killer T (iNKT) cells.

Journal Article Immunology · December 2009 The non-classical major histocompatibility complex (MHC) class I molecule CD1d presents lipid antigens to invariant natural killer T (iNKT) cells, which are an important part of the innate immune system. CD1d/iNKT systems are highly conserved in evolution, ... Full text Link to item Cite

Autophagy is essential for mitochondrial clearance in mature T lymphocytes.

Journal Article J Immunol · April 1, 2009 Featured Publication Macroautophagy plays an important role in the regulation of cell survival, metabolism, and the lysosomal degradation of cytoplasmic material. In the immune system, autophagy contributes to the clearance of intracellular pathogens, MHCII cross-presentation ... Full text Link to item Cite

Differential regulation of phagocyte development by the intrinsic and extrinsic apoptotic pathways

Journal Article EUROPEAN JOURNAL OF CLINICAL INVESTIGATION · April 1, 2009 Link to item Cite

Structure of the F-spondin domain of mindin, an integrin ligand and pattern recognition molecule.

Journal Article EMBO J · February 4, 2009 Featured Publication Mindin (spondin-2) is an extracellular matrix protein of unknown structure that is required for efficient T-cell priming by dendritic cells. Additionally, mindin functions as a pattern recognition molecule for initiating innate immune responses. These dual ... Full text Link to item Cite

Regulation of CD8(+) T cell functions by RARgamma.

Journal Article Semin Immunol · February 2009 Featured Publication Retinoic acid plays a key role in the development and function of the immune system; however, the contribution of each of the three retinoic acid receptors (RARs) to the T cell immune response is not yet well understood. Of these receptors, both RARalpha a ... Full text Link to item Cite

The extracellular matrix protein mindin regulates trafficking of murine eosinophils into the airspace.

Journal Article J Leukoc Biol · January 2009 Asthma remains a major cause of morbidity and hospitalizations in developed nations. Despite the widespread prevalence of this disease, the genetic and environmental factors that mediate development and progression of allergic airways disease remain poorly ... Full text Link to item Cite

Autophagy and lymphocyte homeostasis.

Journal Article Curr Top Microbiol Immunol · 2009 Featured Publication Lymphocyte homeostasis is tightly regulated in vivo by various factors including cytokines, antigens, and costimulatory signals. Central to this regulation is the intricate balance between survival and apoptosis determined by pro- and antiapoptotic factors ... Full text Link to item Cite

Autophagy and lymphocyte homeostasis

Journal Article Current Topics in Microbiology and Immunology · 2009 Lymphocyte homeostasis is tightly regulated in vivo by various factors including cytokines, antigens, and costimulatory signals. Central to this regulation is the intricate balance between survival and apoptosis determined by pro- and antiapoptotic factors ... Full text Cite

A role for cFLIP in B cell proliferation and stress MAPK regulation.

Journal Article J Immunol · January 1, 2009 Fas/Apo-1 signals through the FADD (Fas-associated death domain) adaptor protein, which recruits and activates the apical caspase 8 and leads to apoptosis. Cellular FLIP (cFLIP) is a homolog of caspase 8 and is also capable of binding to FADD. Previous stu ... Full text Link to item Cite

c-FLIP protects mature T lymphocytes from TCR-mediated killing.

Journal Article J Immunol · October 15, 2008 Featured Publication Although c-FLIP has been identified as an important player in the extrinsic (death receptor-induced) apoptosis pathway, its endogenous function in mature T lymphocytes remains undefined. c-FLIP may inhibit or promote T cell death as previous data demonstra ... Full text Link to item Cite

The anti-apoptotic Bcl-2 family member Mcl-1 promotes T lymphocyte survival at multiple stages.

Journal Article J Immunol · July 1, 2008 Featured Publication T lymphocyte development and function are tightly regulated by the intrinsic death pathway through members of the Bcl-2 family. Genetic studies have demonstrated that the Bcl-2 family member Mcl-1 is an important anti-apoptotic protein in the development o ... Full text Link to item Cite

Pattern recognition molecule mindin promotes intranasal clearance of influenza viruses.

Journal Article J Immunol · May 1, 2008 Featured Publication The innate immune response is essential for host defense against microbial pathogen infections and is mediated by pattern recognition molecules recognizing pathogen-associated molecular patterns. Our previous work has demonstrated that the extracellular ma ... Full text Link to item Cite

The long isoform of cellular FLIP is essential for T lymphocyte proliferation through an NF-kappaB-independent pathway.

Journal Article J Immunol · April 15, 2008 Featured Publication Although the long isoform of cellular FLIP (c-FLIP(L)) has been implicated in TCR-mediated signaling, its role in T cell proliferation remains controversial. Some studies have demonstrated that overexpression of c-FLIP(L) promotes T cell proliferation and ... Full text Link to item Cite

The autophagy gene ATG5 plays an essential role in B lymphocyte development.

Journal Article Autophagy · April 2008 Featured Publication Macroautophagy (herein autophagy) is an evolutionarily conserved process, requiring the gene ATG5, by which cells degrade cytoplasmic constituents and organelles. Here we show that ATG5 is required for efficient B cell development and for the maintenance o ... Full text Link to item Cite

Integrin beta 1 regulates phagosome maturation in macrophages through Rac expression.

Journal Article J Immunol · February 15, 2008 Featured Publication Phagocytosis and subsequent phagosome maturation by professional phagocytes are essential in the clearance of infectious microbial pathogens. The molecular regulation of phagosome maturation is largely unknown. We show that integrin beta(1) plays critical ... Full text Link to item Cite

Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes.

Journal Article Autophagy · February 2008 Research in autophagy continues to accelerate,(1) and as a result many new scientists are entering the field. Accordingly, it is important to establish a standard set of criteria for monitoring macroautophagy in different organisms. Recent reviews have des ... Full text Link to item Cite

Defective T cell development and function in the absence of Abelson kinases.

Journal Article J Immunol · December 1, 2007 Thymocyte proliferation, survival, and differentiation are tightly controlled by signaling from the pre-TCR. In this study, we show for the first time that the Abelson (Abl) kinases regulate proximal signaling downstream of the pre-TCR. Conditional deletio ... Full text Link to item Cite

Regulation of innate and adaptive immune responses by a novel pattern recognition molecule mindin

Journal Article Current Immunology Reviews · November 1, 2007 Extracellular matrix proteins play important roles in many different biological processes. Our recent work has discovere important roles for the ECM protein mindin in both innate and adaptive immune responses. Mindin is a member of the F-spondin family of ... Full text Cite

The antiapoptotic protein Mcl-1 is essential for the survival of neutrophils but not macrophages.

Journal Article Blood · February 15, 2007 Featured Publication The antiapoptotic protein Mcl-1, a member of the Bcl-2 family, plays critical roles in promoting the survival of lymphocytes and hematopoietic stem cells. Although previous studies have implicated Mcl-1 in regulating the survival of neutrophils and macroph ... Full text Link to item Cite

Regulation of CD8+ T lymphocyte effector function and macrophage inflammatory cytokine production by retinoic acid receptor gamma.

Journal Article J Immunol · February 15, 2007 Featured Publication Vitamin A and its derivatives regulate a broad array of immune functions. The effects of these retinoids are mediated through members of retinoic acid receptors (RARs) and retinoid X receptors. However, the role of individual retinoid receptors in the plei ... Full text Link to item Cite

A critical role for the autophagy gene Atg5 in T cell survival and proliferation.

Journal Article J Exp Med · January 22, 2007 Featured Publication Macroautophagy (hereafter referred to as autophagy) is a well-conserved intracellular degradation process. Recent studies examining cells lacking the autophagy genes Atg5 and Atg7 have demonstrated that autophagy plays essential roles in cell survival duri ... Full text Link to item Cite

Maintaining T lymphocyte homeostasis: another duty of autophagy.

Journal Article Autophagy · 2007 Featured Publication First identified as a pathway for nutrient recovery during periods of starvation, the role of autophagy has expanded to the clearance of "toxic" intracellular material including ubiquitin-positive protein aggregates, damaged organelles as well as microbial ... Full text Link to item Cite

Efficient dendritic cell priming of T lymphocytes depends on the extracellular matrix protein mindin.

Journal Article EMBO J · September 6, 2006 Featured Publication Rho guanosine triphosphatases (GTPases) regulate multiple aspects of dendritic cell (DC) function, but what regulates the expression of Rho GTPases in DCs is unknown. Here, we show that the extracellular matrix protein mindin regulates the expression of Rh ... Full text Link to item Cite

Toll-like receptor 2-dependent and -independent activation of macrophages by group B streptococci.

Journal Article Immunol Lett · February 15, 2006 Group B streptococcus (GBS), a capsulated gram-positive bacterium, is a major cause of newborn infections. Although the innate immune receptor Toll-like receptor (TLR) 2 has been shown to primarily recognize gram-positive bacterial products, the production ... Full text Link to item Cite

The extracellular matrix protein mindin serves as an integrin ligand and is critical for inflammatory cell recruitment.

Journal Article Blood · December 1, 2005 Featured Publication Leukocyte recruitment to inflammation sites depends on interactions between integrins and extracellular matrix (ECM). In this report we show that mice lacking the ECM protein mindin exhibit severely impaired recruitment of neutrophils and macrophages in 4 ... Full text Link to item Cite

The role of apoptosis in the development and function of T lymphocytes.

Journal Article Cell Res · October 2005 Apoptosis plays an essential role in T cell biology. Thymocytes expressing nonfunctional or autoreactive TCRs are eliminated by apoptosis during development. Apoptosis also leads to the deletion of expanded effector T cells during immune responses. The dys ... Full text Link to item Cite

An essential function for the calcium-promoted Ras inactivator in Fcgamma receptor-mediated phagocytosis.

Journal Article Nat Immunol · September 2005 Featured Publication Fc receptor (FcR)-mediated phagocytosis requires activation of the Rho GTPases Cdc42 and Rac1, but how they are recruited to the FcR is unknown. Here we show that the calcium-promoted Ras inactivator (CAPRI), a Ras GTPase-activating protein, functions as a ... Full text Link to item Cite

An essential role for c-FLIP in the efficient development of mature T lymphocytes.

Journal Article J Exp Med · August 1, 2005 Featured Publication Apoptosis-related genes play important roles in thymocyte maturation. We show that cellular FLICE-like inhibitory protein (c-FLIP), a procaspase-8-like apoptotic regulator, plays an essential role in the efficient development of mature T lymphocytes. Mice ... Full text Link to item Cite

The antiapoptotic protein Bcl-xL is dispensable for the development of effector and memory T lymphocytes.

Journal Article J Immunol · June 1, 2005 Featured Publication The antiapoptotic protein Bcl-x(L) is induced in activated T lymphocytes upon costimulation through CD28, 4-1BB, and OX40. Bcl-x(L) is also highly enriched in memory T lymphocytes. Based on this body of evidence, it was thought that Bcl-x(L) plays an essen ... Full text Link to item Cite

The roles of orphan nuclear receptors in the development and function of the immune system.

Journal Article Cell Mol Immunol · December 2004 Hormones and their receptors regulate cell growth, differentiation and apoptosis and also play important roles in immune function. Recent studies on the subfamily of the orphan nuclear receptors known as retinoid-acid related orphan receptors (ROR) have sh ... Link to item Cite

Lymphocyte development and function in the absence of retinoic acid-related orphan receptor alpha.

Journal Article J Immunol · September 1, 2004 Featured Publication The orphan nuclear receptor, retinoid acid-related orphan receptor (ROR)alpha, is essential for the development of cerebellar Purkinje cells and bone tissue. RORalpha may also play a critical role in lymphocyte development and function because staggerer mi ... Full text Link to item Cite

The extracellular matrix protein mindin is a pattern-recognition molecule for microbial pathogens.

Journal Article Nat Immunol · January 2004 Featured Publication Microbial pathogens use a variety of their surface molecules to bind to host extracellular matrix (ECM) components to establish an effective infection. However, ECM components can also serve as an integral part of the innate immunity. Mice lacking expressi ... Full text Link to item Cite

Lymphocyte accumulation in the spleen of retinoic acid receptor-related orphan receptor gamma-deficient mice.

Journal Article J Immunol · August 15, 2003 Featured Publication The hormone nuclear receptor retinoic acid receptor-related orphan receptor gamma (RORgamma) plays important roles in thymocyte development and lymphoid organogenesis. RORgamma and its thymus-specific isoform RORgammat are expressed in the thymus, but not ... Full text Link to item Cite

Orphan nuclear receptors in T lymphocyte development.

Journal Article J Leukoc Biol · September 2002 Featured Publication Lymphocyte development is initiated from hematopoietic stem cells and can be divided into multiple phenotypically distinct stages. Transcription factors play important roles in programming the developmental process of lymphocytes. Recent studies have ident ... Link to item Cite

Regulation of the TCRalpha repertoire by the survival window of CD4(+)CD8(+) thymocytes.

Journal Article Nat Immunol · May 2002 Featured Publication T cell receptor (TCR) alpha alleles undergo primary and secondary rearrangement in double-positive (DP) thymocytes. By analyzing TCRalpha rearrangement in orphan nuclear receptor RORgamma-deficient mice, in which the DP lifespan is shorter, and in Bcl-x(L) ... Full text Link to item Cite

Down-regulation of the orphan nuclear receptor ROR gamma t is essential for T lymphocyte maturation.

Journal Article J Immunol · June 1, 2000 Featured Publication Thymocyte development is a tightly regulated process. CD4+CD8+ double-positive (DP) immature thymocytes exhibit distinct phenotypic features from mature T cells; they express only 10% of surface TCR that are found on mature T cells and do not proliferate a ... Full text Link to item Cite

The role of orphan nuclear receptor in thymocyte differentiation and lymphoid organ development.

Journal Article Immunol Res · 2000 Featured Publication T lymphocytes differentiate in the thymus through several phenotypically distinct stages that are tightly regulated by multiple nuclear transcription factors. Immature CD4+CD8+ double positive (DP) thymocytes make up a majority of the population in the thy ... Full text Link to item Cite

High level expression of CD43 inhibits T cell receptor/CD3-mediated apoptosis.

Journal Article J Exp Med · December 20, 1999 Featured Publication In a screen designed to identify genes that regulate T cell receptor (TCR)/CD3-mediated apoptosis, we found that high level expression of CD43 protected T cell hybridomas from activation-induced cell death. The protection appears to result from its capacit ... Full text Link to item Cite

Multiple gamma c-dependent cytokines regulate T-cell development.

Journal Article Immunol Today · February 1999 Featured Publication Mutations in the common gamma chain (gamma c) of cytokine receptors account for human X-linked severe combined immunodeficiency disease. gamma c contributes to ligand binding and signaling as a component of five cytokine receptors: interleukin-2-receptor ( ... Full text Link to item Cite

Correlating notch signaling with thymocyte maturation.

Journal Article Immunity · December 1998 Featured Publication The Notch receptor and its ligands are involved in many developmental processes. They are highly expressed in the thymus and have been implicated in the CD4 versus CD8 lineage decision. We identified the constitutively active intracellular fragment of muri ... Full text Link to item Cite

RORgamma t, a novel isoform of an orphan receptor, negatively regulates Fas ligand expression and IL-2 production in T cells.

Journal Article Immunity · December 1998 Featured Publication We have identified RORgamma t, a novel, thymus-specific isoform of the orphan nuclear receptor RORgamma that is expressed predominantly in CD4+ CD8+ double-positive thymocytes. Ectopic expression of RORgamma t protects T cell hybridomas from activation-ind ... Full text Link to item Cite

Monoclonal antibodies to the common gamma-chain as cytokine receptor antagonists in vivo: effect on intrathymic and intestinal intraepithelial T lymphocyte development.

Journal Article J Leukoc Biol · June 1998 Featured Publication Mice lacking a functional gamma c subunit of cytokine receptors exhibit profound defects in the development of multiple lymphoid lineages. To investigate the role of gamma c-dependent cytokines in T cell development, the phenotype of developing T cells was ... Full text Link to item Cite

The structure and function of gamma c-dependent cytokines and receptors: regulation of T lymphocyte development and homeostasis.

Journal Article Crit Rev Immunol · 1998 Featured Publication Five cytokines, IL-2, IL-4, IL-7, IL-9, and IL-15, form one group that is characterized by utilizing the common gamma chain (gamma c) as a receptor subunit. Examination of the phenotype of various cytokine or cytokine receptor "knockout" mice demonstrates ... Full text Link to item Cite

Rotavirus RNA polymerase requires the core shell protein to synthesize the double-stranded RNA genome.

Journal Article J Virol · December 1997 Rotavirus cores contain the double-stranded RNA (dsRNA) genome, RNA polymerase VP1, and guanylyltransferase VP3 and are enclosed within a lattice formed by the RNA-binding protein VP2. Analysis of baculovirus-expressed core-like particles (CLPs) has shown ... Full text Link to item Cite

The common gamma-chain of cytokine receptors regulates intrathymic T cell development at multiple stages.

Journal Article J Immunol · March 15, 1997 Featured Publication Signaling through the common gamma chain (gamma c), a subunit of the receptors for IL-2, -4, -7, -9, and -15, is critical for lymphocyte development, with the IL-7/IL-7R representing one important interaction. To investigate the stages of intrathymic T cel ... Link to item Cite

Interleukin-7 receptor alpha is essential for the development of gamma delta + T cells, but not natural killer cells.

Journal Article J Exp Med · July 1, 1996 Featured Publication Mice that lack a functional gamma c subunit of the receptors for interleukin (IL)-2, IL-4, IL-7, IL-9, and IL-15 display profound defects in lymphoid development. The IL-7/IL-7R system represents a critical interaction for conventional T and B cell develop ... Full text Link to item Cite

The IL-2 receptor gamma c chain does not function as a subunit shared by the IL-4 and IL-13 receptors. Implication for the structure of the IL-4 receptor.

Journal Article J Immunol · July 1, 1995 Featured Publication The IL-2 receptor (IL-2R) gamma c subunit is also a component of the receptors for IL-4, IL-7, IL-9, and IL-15. The IL-4R and IL-13R appear to share a common subunit, and gamma c was proposed to be this shared subunit. In this study, we have assessed the r ... Link to item Cite

Blockade of T- and B-lymphocyte development by antibody to the gamma c subunit of the receptors for interleukins 2, 4, and 7.

Journal Article Proc Natl Acad Sci U S A · June 6, 1995 Featured Publication Cytokines are important regulators of hematopoesis. Mutations in gamma c, which is a subunit shared by the receptors for interleukin (IL) 2, IL-4, and IL-7, have been causally associated with human X chromosome-linked severe combined immunodeficiency disea ... Full text Link to item Cite

Biochemical identity and characterization of the mouse interleukin-2 receptor beta and gamma c subunits.

Journal Article J Interferon Cytokine Res · May 1995 Featured Publication Although the mouse IL-2 receptor (IL-2R) beta and gamma c subunits have been identified by molecular cloning, the biochemical identity of these subunits has not yet been established. In the present study, the mouse IL-2R was biochemically characterized fro ... Full text Link to item Cite

Expression and function of the gamma c subunit of the IL-2, IL-4, and IL-7 receptors. Distinct interaction of gamma c in the IL-4 receptor.

Journal Article J Immunol · February 15, 1995 Featured Publication IL-2R, IL-4R, and IL-7R share a common subunit referred to as gamma c and the IL-13R has been proposed to contain gamma c as a subunit. In this report we have used two novel mAbs (3E12 and 4G3) to distinct epitopes of mouse gamma c to determine its lymphoi ... Link to item Cite