Xiaoping Zhong

Journal article J Cereb Blood Flow Metab · June 2025 Cardiac arrest (CA) is a life-threatening condition that requires immediate medical attention. Considerable advances in resuscitation have led to an increasing number of patients who survive the initial arrest event. However, among this growing patient pop ... Full text Link to item Cite

DGKα and ζ Deficiency Causes Regulatory T-Cell Dysregulation, Destabilization, and Conversion to Pathogenic T-Follicular Helper Cells to Trigger IgG1-Predominant Autoimmunity.

Journal article bioRxiv · May 19, 2025 Regulatory T cells (Tregs) actively engage in immune suppression to prevent autoimmune diseases but also inhibit anti-tumor immunity. Although Tregs express a TCR repertoire with relatively high affinities to self, they are normally quite stable and their ... Full text Link to item Cite

Microglial heterogeneity in the ischemic stroke mouse brain of both sexes.

Journal article Genome Med · August 2, 2024 BACKGROUND: Ischemic stroke elicits a complex and sustained immune response in the brain. Immunomodulatory treatments have long held promise for improving stroke outcomes, yet none have succeeded in the clinical setting. This lack of success is largely due ... Full text Link to item Cite

Development and Evaluation of a Novel Mouse Model of Asphyxial Cardiac Arrest Revealed Severely Impaired Lymphopoiesis After Resuscitation.

Journal article J Am Heart Assoc · June 2021 Background Animal disease models represent the cornerstone in basic cardiac arrest (CA) research. However, current experimental models of CA and resuscitation in mice are limited. In this study, we aimed to develop a mouse model of asphyxial CA followed by ... Full text Open Access Link to item Cite

Differential controls of MAIT cell effector polarization by mTORC1/mTORC2 via integrating cytokine and costimulatory signals.

Journal article Nat Commun · April 1, 2021 Mucosal-associated invariant T (MAIT) cells have important functions in immune responses against pathogens and in diseases, but mechanisms controlling MAIT cell development and effector lineage differentiation remain unclear. Here, we report that IL-2/IL-1 ... Full text Open Access Link to item Cite

Thymic Epithelial Cell-Derived IL-15 and IL-15 Receptor α Chain Foster Local Environment for Type 1 Innate Like T Cell Development.

Journal article Front Immunol · 2021 Expression of tissue-restricted antigens (TRAs) in thymic epithelial cells (TECs) ensures negative selection of highly self-reactive T cells to establish central tolerance. Whether some of these TRAs could exert their canonical biological functions to shap ... Full text Link to item Cite

Regulation of Intrinsic and Bystander T Follicular Helper Cell Differentiation and Autoimmunity by Tsc1.

Journal article Front Immunol · 2021 T Follicular helper (Tfh) cells promote germinal center (GC) B cell responses to develop effective humoral immunity against pathogens. However, dysregulated Tfh cells can also trigger autoantibody production and the development of autoimmune diseases. We r ... Full text Link to item Cite

Loss of Diacylglycerol Kinase α Enhances Macrophage Responsiveness.

Journal article Front Immunol · 2021 The diacylglycerol kinases (DGKs) are a family of enzymes responsible for the conversion of diacylglycerol (DAG) to phosphatidic acid (PA). In addition to their primary function in lipid metabolism, DGKs have recently been identified as potential therapeut ... Full text Link to item Cite

Negative control of diacylglycerol kinase ζ-mediated inhibition of T cell receptor signaling by nuclear sequestration in mice.

Journal article Eur J Immunol · November 2020 Diacylglycerol kinases (DGKs) play important roles in restraining diacylglycerol (DAG)-mediated signaling. Within the DGK family, the ζ isoform appears to be the most important isoform in T cells for controlling their development and function. DGKζ has bee ... Full text Link to item Cite

MxA suppresses TAK1-IKKα/β-NF-κB mediated inflammatory cytokine production to facilitate Mycobacterium tuberculosis infection.

Journal article J Infect · August 2020 OBJECTIVES: Interferons (IFNs) play multifunctional roles in host defense against infectious diseases by inducing IFN-stimulated genes (ISGs). However, little is known about how ISGs regulate host immune response to Mycobacterium tuberculosis (Mtb) infecti ... Full text Link to item Cite

A Novel Method for the Prenatal Diagnosis of Cleft Palate Based on Amniotic Fluid Metabolites

Journal article Chinese Journal of Plastic and Reconstructive Surgery · June 1, 2020 Background and purpose: The prenatal diagnosis of cleft palate is an important component of sequential therapy, but the relevant diagnostic methods are still limited. We aimed here, to explore the possibility of an early prenatal diagnosis of cleft palate ... Full text Cite

Graded diacylglycerol kinases α and ζ activities ensure mucosal-associated invariant T-cell development in mice.

Journal article Eur J Immunol · February 2020 Mucosal-associated invariant T (MAIT) cells participate in both protective immunity and pathogenesis of diseases. Most murine MAIT cells express an invariant TCRVα19-Jα33 (iVα19) TCR, which triggers signals crucial for their development. However, signal pa ... Full text Link to item Cite

MiR-106a-5p modulates apoptosis and metabonomics changes by TGF-β/Smad signaling pathway in cleft palate.

Journal article Exp Cell Res · January 15, 2020 BACKGROUND: The molecular mechanisms of abnormal palatogenesis were investigated in this study. A key regulator, miR-106a-5p, and its target pathway were analyzed. OBJECTIVES: This research is trying to clarify the underlying mechanism of the modulation of ... Full text Link to item Cite

Multi‑organ assessment via a 9.4‑Tesla MRS evaluation of metabolites during the embryonic development of cleft palate induced by dexamethasone.

Journal article Mol Med Rep · October 2019 The aim of the present study was to determine the association between maternal metabolism and development of the fetal palate, and to suggest a potential non‑invasive prenatal diagnostic method for fetal cleft palate (CP). Dexamethasone (DXM) was used to c ... Full text Link to item Cite

Efficient CD4Cre-Mediated Conditional KRas Expression in Alveolar Macrophages and Alveolar Epithelial Cells Causes Fatal Hyperproliferative Pneumonitis.

Journal article J Immunol · September 1, 2019 The CD4Cre transgenic model has been widely used for T cell-specific gene manipulation. We report unexpected highly efficient Cre-mediated recombination in alveolar macrophages (AMFs), bronchial epithelial cells (BECs), and alveolar epithelial cells (AECs) ... Full text Link to item Cite

NLRC3 expression in dendritic cells attenuates CD4+ T cell response and autoimmunity.

Journal article EMBO J · August 15, 2019 NOD-like receptor (NLR) family CARD domain containing 3 (NLRC3), an intracellular member of NLR family, is a negative regulator of inflammatory signaling pathways in innate and adaptive immune cells. Previous reports have shown that NLRC3 is expressed in d ... Full text Link to item Cite

Deficiency of Mucosal-Associated Invariant T Cells in TCRJα18 Germline Knockout Mice.

Journal article Immunohorizons · June 11, 2019 Mucosal-associated invariant T (MAIT) cells and invariant NK T (iNKT) cells account for the major lymphocyte populations that express invariant TCRα-chains. MAIT cells mostly express the TCRVα19-Jα33 TCR in mice and the TCRVα7.2-Jα33 TCR in humans, whereas ... Full text Link to item Cite

NCKAP1 improves patient outcome and inhibits cell growth by enhancing Rb1/p53 activation in hepatocellular carcinoma.

Journal article Cell Death Dis · May 8, 2019 In our previous report, we identified miR-34c-3p as an independent factor contributing to the carcinogenesis of hepatocellular carcinoma (HCC) by targeting NCK Associated Protein 1 (NCKAP1). NCKAP1 has been known to promote the malignancy of cancer cells b ... Full text Link to item Cite

Circulating Mucosal-Associated Invariant T Cells in a Large Cohort of Healthy Chinese Individuals From Newborn to Elderly.

Journal article Front Immunol · 2019 Mucosal-associated invariant T (MAIT) cells, which are enriched in human blood and express a semi-invariant TCR chain, play important roles in conditions such as infectious diseases and cancer. The influence of age on levels and functional characteristics ... Full text Link to item Cite

Differential Control of iNKT Cell Effector Lineage Differentiation by the Forkhead Box Protein O1 (Foxo1) Transcription Factor.

Journal article Frontiers in immunology · January 2019 The invariant NKT (iNKT) cells recognize glycolipid antigens presented by the non-classical MHC like molecule CD1d. They represent an innate T-cell lineage with the ability to rapidly produce a variety of cytokines in response to agonist stimulation ... Full text Cite

DGK α and ζ Activities Control TH1 and TH17 Cell Differentiation.

Journal article Front Immunol · 2019 CD4+ T helper (TH) cells are critical for protective adaptive immunity against pathogens, and they also contribute to the pathogenesis of autoimmune diseases. How TH differentiation is regulated by the TCR's downstream signaling is still poorly understood. ... Full text Link to item Cite

Thymic Epithelial Cells Contribute to Thymopoiesis and T Cell Development.

Journal article Front Immunol · 2019 The thymus is the primary lymphoid organ responsible for the generation and maturation of T cells. Thymic epithelial cells (TECs) account for the majority of thymic stromal components. They are further divided into cortical and medullary TECs based on thei ... Full text Link to item Cite

Risk factors of extra-hepatic progression after transarterial chemoembolization for hepatocellular carcinoma patients: A retrospective study in 654 cases

Journal article Journal of Cancer · January 1, 2019 Aim: To investigate the risk factors of extra-hepatic progression after TACE in HCC. Methods: The study population included 654 HCC patients who underwent TACE between October 2005 and September 2012. We collected and analyzed their clinical characteristic ... Full text Cite

Anatomical versus non-anatomical resection for hepatocellular carcinoma with microscope vascular invasion: A propensity score matching analysis

Journal article Journal of Cancer · January 1, 2019 Background: The benefits of anatomical resection (AR) and non-anatomical resection (NAR) on hepatocellular carcinoma (HCC) patients with microscope vascular invasion (MVI) remain unknown. We aimed to investigate the prognostic outcomes of AR and NAR for HC ... Full text Cite

NLRC3 negatively regulates CD4+ T cells and impacts protective immunity during Mycobacterium tuberculosis infection.

Journal article PLoS Pathog · August 2018 NLRC3, a member of the NLR family, has been reported as a negative regulator of inflammatory signaling pathways in innate immune cells. However, the direct role of NLRC3 in modulation of CD4+ T-cell responses in infectious diseases has not been studied. In ... Full text Link to item Cite

Vitamin B5 Reduces Bacterial Growth via Regulating Innate Immunity and Adaptive Immunity in Mice Infected with Mycobacterium tuberculosis.

Journal article Front Immunol · 2018 The mechanisms by which vitamins regulate immunity and their effect as an adjuvant treatment for tuberculosis have gradually become very important research topics. Studies have found that vitamin B5 (VB5) can promote epithelial cells to express inflammator ... Full text Link to item Cite

Vitamin B1 Helps to Limit Mycobacterium tuberculosis Growth via Regulating Innate Immunity in a Peroxisome Proliferator-Activated Receptor-γ-Dependent Manner.

Journal article Front Immunol · 2018 It is known that vitamin B1 (VB1) has a protective effect against oxidative retinal damage induced by anti-tuberculosis drugs. However, it remains unclear whether VB1 regulates immune responses during Mycobacterium tuberculosis (MTB) infection. We report h ... Full text Link to item Cite

IL-17 Production of Neutrophils Enhances Antibacteria Ability but Promotes Arthritis Development During Mycobacterium tuberculosis Infection.

Journal article EBioMedicine · September 2017 To our knowledge, no studies have examined the role of IL-17 production by neutrophils in immune defense against Mycobacterium tuberculosis (MTB) infection and the pathogenesis of rheumatoid arthritis (RA) caused by MTB infection. Here, we determined that ... Full text Link to item Cite

Essential Role of mTORC1 in Self-Renewal of Murine Alveolar Macrophages.

Journal article J Immunol · January 1, 2017 Alveolar macrophages (AMϕ) have the capacity of local self-renewal through adult life; however, mechanisms that regulate AMϕ self-renewal remain poorly understood. We found that myeloid-specific deletion of Raptor, an essential component of the mammalian/m ... Full text Link to item Cite

Vibrio vulnificus induces mTOR activation and inflammatory responses in macrophages.

Journal article PLoS One · 2017 Vibrio vulnificus (V. vulnificus), a Gram-negative marine bacterium, can cause life-threatening primary septicemia, especially in patients with liver diseases. How V. vulnificus affects the liver and how it acts on macrophages are not well understood. In t ... Full text Link to item Cite

Cervical spinal functional magnetic resonance imaging of the spinal cord injured patient during electrical stimulation.

Journal article Eur Spine J · January 2017 PURPOSE: To evaluate the spatial distribution and signal intensity changes following spinal cord activation in patients with spinal cord injury. METHODS: This study used spinal functional magnetic resonance imaging (fMRI) based on signal enhancement by ext ... Full text Link to item Cite

mTOR is critical for intestinal T-cell homeostasis and resistance to Citrobacter rodentium.

Journal article Sci Rep · October 12, 2016 T-cells play an important role in promoting mucosal immunity against pathogens, but the mechanistic basis for their homeostasis in the intestine is still poorly understood. We report here that T-cell-specific deletion of mTOR results in dramatically decrea ... Full text Link to item Cite

Critical roles of mTOR Complex 1 and 2 for T follicular helper cell differentiation and germinal center responses.

Journal article Elife · September 30, 2016 T follicular helper (Tfh) cells play critical roles for germinal center responses and effective humoral immunity. We report here that mTOR in CD4 T cells is essential for Tfh differentiation. In Mtorf/f-Cd4Cre mice, both constitutive and inducible Tfh diff ... Full text Link to item Cite

Sustained activation of mTORC1 in macrophages increases AMPKα-dependent autophagy to maintain cellular homeostasis.

Journal article BMC Biochem · July 7, 2016 BACKGROUND: The mechanistic target of rapamycin complex 1 (mTORC1) is a well-conserved serine/threonine protein kinase that controls autophagy as well as many other processes such as protein synthesis, cell growth, and metabolism. The activity of mTORC1 is ... Full text Link to item Cite

Dominant Splice Site Mutations in PIK3R1 Cause Hyper IgM Syndrome, Lymphadenopathy and Short Stature.

Journal article J Clin Immunol · July 2016 The purpose of this research was to use next generation sequencing to identify mutations in patients with primary immunodeficiency diseases whose pathogenic gene mutations had not been identified. Remarkably, four unrelated patients were found by next gene ... Full text Open Access Link to item Cite

mTORC2 in Thymic Epithelial Cells Controls Thymopoiesis and T Cell Development.

Journal article J Immunol · July 1, 2016 Thymic epithelial cells (TECs) play important roles in T cell generation. Mechanisms that control TEC development and function are still not well defined. The mammalian or mechanistic target of rapamycin complex (mTORC)2 signals to regulate cell survival, ... Full text Link to item Cite

Unexpected positive control of NFκB and miR-155 by DGKα and ζ ensures effector and memory CD8+ T cell differentiation.

Journal article Oncotarget · June 7, 2016 Signals from the T-cell receptor (TCR) and γ-chain cytokine receptors play crucial roles in initiating activation and effector/memory differentiation of CD8 T-cells. We report here that simultaneous deletion of both diacylglycerol kinase (DGK) α and ζ (DKO ... Full text Link to item Cite

mTORC1 in Thymic Epithelial Cells Is Critical for Thymopoiesis, T-Cell Generation, and Temporal Control of γδT17 Development and TCRγ/δ Recombination.

Journal article PLoS Biol · February 2016 Thymus is crucial for generation of a diverse repertoire of T cells essential for adaptive immunity. Although thymic epithelial cells (TECs) are crucial for thymopoiesis and T cell generation, how TEC development and function are controlled is poorly under ... Full text Link to item Cite

Intercellular Protein Transfer from Thymocytes to Thymic Epithelial Cells.

Journal article PLoS One · 2016 Promiscuous expression of tissue restricted antigens (TRAs) in medullary thymic epithelial cells (mTECs) is crucial for negative selection of self-reactive T cells to establish central tolerance. Intercellular transfer of self-peptide-MHC complexes from mT ... Full text Open Access Link to item Cite

Diacylglycerol Kinases in T Cell Tolerance and Effector Function.

Journal article Front Cell Dev Biol · 2016 Diacylglycerol kinases (DGKs) are a family of enzymes that regulate the relative levels of diacylglycerol (DAG) and phosphatidic acid (PA) in cells by phosphorylating DAG to produce PA. Both DAG and PA are important second messengers cascading T cell recep ... Full text Link to item Cite

mTOR and its tight regulation for iNKT cell development and effector function.

Journal article Mol Immunol · December 2015 Invariant NKT (iNKT) cells, which express the invariant Vα14Jα18 TCR that recognizes lipid antigens, have the ability to rapidly respond to agonist stimulation, producing a variety of cytokines that can shape both innate and adaptive immunity. iNKT cells h ... Full text Link to item Cite

TSC1 Promotes B Cell Maturation but Is Dispensable for Germinal Center Formation.

Journal article PLoS One · 2015 Accumulating evidence indicates that the tuberous sclerosis complex 1 (TSC1), a tumor suppressor that acts by inhibiting mTOR signaling, plays an important role in the immune system. We report here that TSC1 differentially regulates mTOR complex 1 (mTORC1) ... Full text Open Access Link to item Cite

IKKα negatively regulates ASC-dependent inflammasome activation.

Journal article Nat Commun · September 30, 2014 The inflammasomes are multiprotein complexes that activate caspase-1 in response to infections and stress, resulting in the secretion of pro-inflammatory cytokines. Here we report that IκB kinase α (IKKα) is a critical negative regulator of apoptosis-assoc ... Full text Link to item Cite

A nonsense mutation in IKBKB causes combined immunodeficiency.

Journal article Blood · September 25, 2014 Identification of the molecular etiologies of primary immunodeficiencies has led to important insights into the development and function of the immune system. We report here the cause of combined immunodeficiency in 4 patients from 2 different consanguineo ... Full text Link to item Cite

Role of tumor suppressor TSC1 in regulating antigen-specific primary and memory CD8 T cell responses to bacterial infection.

Journal article Infect Immun · July 2014 The serine/threonine kinase mammalian/mechanistic target of rapamycin (mTOR) integrates various environmental cues such as the presence of antigen, inflammation, and nutrients to regulate T cell growth, metabolism, and function. The tuberous sclerosis 1 (T ... Full text Link to item Cite

T cell receptor-dependent activation of mTOR signaling in T cells is mediated by Carma1 and MALT1, but not Bcl10.

Journal article Sci Signal · June 10, 2014 Signaling to the mechanistic target of rapamycin (mTOR) regulates diverse cellular processes, including protein translation, cellular proliferation, metabolism, and autophagy. Most models place Akt upstream of the mTOR complex, mTORC1; however, in T cells, ... Full text Link to item Cite

iNKT cells require TSC1 for terminal maturation and effector lineage fate decisions.

Journal article J Clin Invest · April 2014 Terminal maturation of invariant NKT (iNKT) cells from stage 2 (CD44+NK1.1-) to stage 3 (CD44+NK1.1+) is accompanied by a functional acquisition of a predominant IFN-γ-producing (iNKT-1) phenotype; however, some cells develop into IL-17-producing iNKT (iNK ... Full text Link to item Cite

Tuberous sclerosis 1 promotes invariant NKT cell anergy and inhibits invariant NKT cell-mediated antitumor immunity.

Journal article J Immunol · March 15, 2014 Development of effective immune therapies for cancer patients requires better understanding of hurdles that prevent the generation of effective antitumor immune responses. Administration of α-galactosylceramide (α-GalCer) in animals enhances antitumor immu ... Full text Link to item Cite

Mechanistic target of rapamycin complex 1 is critical for invariant natural killer T-cell development and effector function.

Journal article Proc Natl Acad Sci U S A · February 25, 2014 The mechanisms that control invariant natural killer T (iNKT)-cell development and function are still poorly understood. The mechanistic or mammalian target of rapamycin (mTOR) integrates various environmental signals/cues to regulate cell growth, prolifer ... Full text Link to item Cite

The role of diacylglycerol kinase ζ and phosphatidic acid in the mechanical activation of mammalian target of rapamycin (mTOR) signaling and skeletal muscle hypertrophy.

Journal article J Biol Chem · January 17, 2014 The activation of mTOR signaling is essential for mechanically induced changes in skeletal muscle mass, and previous studies have suggested that mechanical stimuli activate mTOR (mammalian target of rapamycin) signaling through a phospholipase D (PLD)-depe ... Full text Link to item Cite

Diacylglycerol kinase ζ limits B cell antigen receptor-dependent activation of ERK signaling to inhibit early antibody responses.

Journal article Sci Signal · October 15, 2013 Signaling downstream of the B cell antigen receptor (BCR) is tightly regulated to enable cells to gauge the strength and duration of antigen-receptor interactions and to respond appropriately. We investigated whether metabolism of the second messenger diac ... Full text Link to item Cite

Critical role of the tumor suppressor tuberous sclerosis complex 1 in dendritic cell activation of CD4 T cells by promoting MHC class II expression via IRF4 and CIITA.

Journal article J Immunol · July 15, 2013 Dendritic cell (DC) maturation is characterized by upregulation of cell-surface MHC class II (MHC-II) and costimulatory molecules, and production of a variety of cytokines that can shape both innate and adaptive immunity. Paradoxically, transcription of th ... Full text Link to item Cite

Type B CpG oligodeoxynucleotides induce Th1 responses to peanut antigens: modulation of sensitization and utility in a truncated immunotherapy regimen in mice.

Journal article Mol Nutr Food Res · May 2013 SCOPE: Peanut allergy stems from a Th2-biased immune response to peanut allergens leading to IgE production and allergic reactions upon ingestion. METHODS AND RESULTS: A model of peanut allergy in C3H/HeJ mice was used to assess whether type A, B, or C CpG ... Full text Link to item Cite

Mnk1 and 2 are dispensable for T cell development and activation but important for the pathogenesis of experimental autoimmune encephalomyelitis.

Journal article J Immunol · February 1, 2013 T cell development and activation are usually accompanied by expansion and production of numerous proteins that require active translation. The eukaryotic translation initiation factor 4E (eIF4E) binds to the 5' cap structure of mRNA and is critical for ca ... Full text Link to item Cite

Negative control of mast cell degranulation and the anaphylactic response by the phosphatase lipin1.

Journal article Eur J Immunol · January 2013 Mast cells play a critical role in the pathogenesis of allergic diseases; however, how mast cell function is regulated is still not well understood. Both phosphatidic acid (PA) and diacylglycerol (DAG) are important secondary messengers involved in mast ce ... Full text Link to item Cite

Role of diacylglycerol kinases in T cell development and function.

Journal article Crit Rev Immunol · 2013 Diacylglycerol (DAG), a second messenger generated by phospholipase Cγ1 activity upon engagement of a T-cell receptor, triggers several signaling cascades that play important roles in T cell development and function. A family of enzymes called DAG kinases ... Full text Link to item Cite

Diacylglycerol kinase zeta positively controls the development of iNKT-17 cells.

Journal article PLoS One · 2013 Invariant natural killer T (iNKT) cells play important roles in bridging innate and adaptive immunity via rapidly producing a variety of cytokines. A small subset of iNKT cells produces IL-17 and is generated in the thymus during iNKT-cell ontogeny. The me ... Full text Link to item Cite

Regulation of Lipid Signaling by Diacylglycerol Kinases during T Cell Development and Function.

Journal article Front Immunol · 2013 Diacylglycerol (DAG) and phosphatidic acid (PA) are bioactive lipids synthesized when the T cell receptor binds to a cognate peptide-MHC complex. DAG triggers signaling by recruiting Ras guanyl-releasing protein 1, PKCθ, and other effectors, whereas PA bin ... Full text Link to item Cite

MicroRNA-34a enhances T cell activation by targeting diacylglycerol kinase ζ.

Journal article PLoS One · 2013 The engagement of the T cell receptor (TCR) induces the generation of diacylglycerol (DAG), an important second messenger activating both the Ras/Erk and PKCθ/NFκB pathways. DAG kinases (DGKs) participate in the metabolism of DAG by converting it to phosph ... Full text Link to item Cite

An expanded role of the tumor suppressor TSC1 in T cell tolerance.

Journal article Cell Cycle · November 1, 2012 Full text Link to item Cite

FoxO-dependent regulation of diacylglycerol kinase α gene expression.

Journal article Mol Cell Biol · October 2012 Diacylglycerol kinase α (DGKα) regulates diacylglycerol levels, catalyzing its conversion into phosphatidic acid. The α isoform is central to immune response regulation; it downmodulates Ras-dependent pathways and is necessary for establishment of the unre ... Full text Link to item Cite

Pepsinized cashew proteins are hypoallergenic and immunogenic and provide effective immunotherapy in mice with cashew allergy.

Journal article J Allergy Clin Immunol · September 2012 BACKGROUND: IgE-mediated allergic reactions to cashews and other nuts can trigger life-threatening anaphylaxis. Proactive therapies to decrease reaction severity do not exist. OBJECTIVES: We aimed to determine the efficacy of pepsin-digested cashew protein ... Full text Link to item Cite

Tumor suppressor TSC1 is critical for T-cell anergy.

Journal article Proc Natl Acad Sci U S A · August 28, 2012 T-cell anergy is a state of T cells that is hyporesponsive to stimulation via the T-cell receptor and costimulatory molecules and is thought to be important for self-tolerance. How T-cell anergy is regulated is still poorly understood. We report here that ... Full text Link to item Cite

Chronic activation of the kinase IKKβ impairs T cell function and survival.

Journal article J Immunol · August 1, 2012 Activation of the transcription factor NF-κB is critical for cytokine production and T cell survival after TCR engagement. The effects of persistent NF-κB activity on T cell function and survival are poorly understood. In this study, using a murine model t ... Full text Link to item Cite

Differential requirement of RasGRP1 for γδ T cell development and activation.

Journal article J Immunol · July 1, 2012 γδ T (γδT) cells belong to a distinct T cell lineage that performs immune functions different from αβ T (αβT) cells. Previous studies established that Erk1/2 MAPKs are critical for positive selection of αβT cells. Additional evidence suggests that increase ... Full text Link to item Cite

CD45-deficient severe combined immunodeficiency caused by uniparental disomy.

Journal article Proc Natl Acad Sci U S A · June 26, 2012 Analysis of the molecular etiologies of SCID has led to important insights into the control of immune cell development. Most cases of SCID result from either X-linked or autosomal recessive inheritance of mutations in a known causative gene. However, in so ... Full text Link to item Cite

The role and regulation of mTOR in T-lymphocyte function.

Journal article Arch Immunol Ther Exp (Warsz) · June 2012 The conversion of naïve T cells into effector T cells is initiated by stimulation through the T-cell receptor (TCR). Upon activation, T cells undergo significant morphological and functional changes, putting new metabolic demands on the cell. Past research ... Full text Link to item Cite

The role of tuberous sclerosis complex 1 in regulating innate immunity.

Journal article J Immunol · April 15, 2012 The mechanisms that control TLR-induced responses, including endotoxin tolerance, have been not well understood. The tuberous sclerosis complex 1 (TSC1) is a tumor suppressor that inhibits the mammalian target of rapamycin (mTOR). We show in this study tha ... Full text Link to item Cite

Regulation of mast cell survival and function by tuberous sclerosis complex 1.

Journal article Blood · April 5, 2012 Mast cells play critical roles in allergic disorders and asthma. The importance of tuberous sclerosis complex 1/2-mammalian target of rapamycin (TSC1/2-mTOR) signaling in mast cells is unknown. Here, we report that TSC1 is a critical regulator for mTOR sig ... Full text Link to item Cite

Differential regulation of primary and memory CD8 T cell immune responses by diacylglycerol kinases.

Journal article J Immunol · March 1, 2012 The manipulation of signals downstream of the TCR can have profound consequences for T cell development, function, and homeostasis. Diacylglycerol (DAG) produced after TCR stimulation functions as a secondary messenger and mediates the signaling to Ras-MEK ... Full text Link to item Cite

Murine regulatory T cells contain hyperproliferative and death-prone subsets with differential ICOS expression.

Journal article J Immunol · February 15, 2012 Regulatory T cells (Treg) are crucial for self-tolerance. It has been an enigma that Treg exhibit an anergic phenotype reflected by hypoproliferation in vitro after TCR stimulation but undergo vigorous proliferation in vivo. We report in this study that mu ... Full text Link to item Cite

Peanut allergen Ara h 2-specific T cells are activated via Ras-Erk MAP kinase pathway signalling and identified by CD154 expression

Journal article Food and Agricultural Immunology · December 1, 2011 Background. Peanut allergy is driven by peanut-specific Th2 cells. Ara h 2, a peanut 2S albumin, is one of the major peanut allergens. Methods. An Ara h 2-specific T cell line was generated from peanut sensitised C3H/HeJ mice and used to analyse allergen-i ... Full text Cite

SAP-mediated inhibition of diacylglycerol kinase α regulates TCR-induced diacylglycerol signaling.

Journal article J Immunol · December 1, 2011 Diacylglycerol kinases (DGKs) metabolize diacylglycerol to phosphatidic acid. In T lymphocytes, DGKα acts as a negative regulator of TCR signaling by decreasing diacylglycerol levels and inducing anergy. In this study, we show that upon costimulation of th ... 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

Critical roles of RasGRP1 for invariant NKT cell development.

Journal article J Immunol · November 1, 2011 The invariant NKT (iNKT) cell lineage contains CD4(+) and CD4(-) subsets. The mechanisms that control such subset differentiation and iNKT cell maturation in general have not been fully understood. RasGRP1, a guanine nucleotide exchange factor for TCR-indu ... Full text Link to item Cite

Tight regulation of diacylglycerol-mediated signaling is critical for proper invariant NKT cell development.

Journal article J Immunol · September 1, 2011 Type I NKT cells, or invariant NKT (iNKT) cells, express a semi-invariant TCR characterized by its unique Vα14-Jα18 usage (iVα14TCR). Upon interaction with glycolipid/CD1d complexes, the iVα14TCRs transduce signals that are essential for iNKT selection and ... Full text Link to item Cite

Diacylglycerol kinase ζ deficiency in a non-CD4(+) T-cell compartment leads to increased peanut hypersensitivity.

Journal article J Allergy Clin Immunol · July 2011 Peanut sensitization in diacylglycerol kinase zeta (DGKζ) deficient mice led to elevated peanut-IgE levels and severe anaphylaxis. DGKζ deficient CD4+T cells did not account for the phenotype. Future studies will determine which immune lineage caused incre ... Full text Link to item Cite

Negative regulation of mTOR activation by diacylglycerol kinases.

Journal article Blood · April 14, 2011 The engagement of TCR induces T-cell activation, which initiates multiple characteristic changes such as increase in cell size, cell division, and the production of cytokines and other effector molecules. The mammalian target of rapamycin (mTOR) regulates ... Full text Link to item Cite

Receptor signaling in immune cell development and function.

Journal article Immunol Res · April 2011 Immune cell development and function must be tightly regulated through cell surface receptors to ensure proper responses to pathogen and tolerance to self. In T cells, the signal from the T-cell receptor is essential for T-cell maturation, homeostasis, and ... Full text Link to item Cite

Clinical efficacy and immune regulation with peanut oral immunotherapy.

Journal article J Allergy Clin Immunol · August 2009 BACKGROUND: Oral immunotherapy (OIT) has been thought to induce clinical desensitization to allergenic foods, but trials coupling the clinical response and immunologic effects of peanut OIT have not been reported. OBJECTIVE: The study objective was to inve ... Full text Link to item Cite

Synaptic removal of diacylglycerol by DGKzeta and PSD-95 regulates dendritic spine maintenance.

Journal article EMBO J · April 22, 2009 Diacylglycerol (DAG) is an important lipid signalling molecule that exerts an effect on various effector proteins including protein kinase C. A main mechanism for DAG removal is to convert it to phosphatidic acid (PA) by DAG kinases (DGKs). However, it is ... Full text Link to item Cite

Diacylglycerol kinase zeta regulates actin cytoskeleton reorganization through dissociation of Rac1 from RhoGDI.

Journal article Mol Biol Cell · April 2009 Activation of Rac1 GTPase signaling is stimulated by phosphorylation and release of RhoGDI by the effector p21-activated kinase 1 (PAK1), but it is unclear what initiates this potential feed-forward mechanism for regulation of Rac activity. Phosphatidic ac ... Full text Link to item Cite

Synergistic control of T cell development and tumor suppression by diacylglycerol kinase alpha and zeta.

Journal article Proc Natl Acad Sci U S A · August 19, 2008 Diacylglycerol (DAG) kinases (DGKs) are a family of enzymes that convert DAG to phosphatidic acid (PA), the physiologic functions of which have been poorly defined. We report here that DGK alpha and zeta synergistically promote T cell maturation in the thy ... Full text Link to item Cite

Diacylglycerol kinases in immune cell function and self-tolerance.

Journal article Immunol Rev · August 2008 Both diacylglycerol (DAG) and phosphatidic acid (PA) are important second messengers involved in signal transduction from many immune cell receptors and can be generated and metabolized through multiple mechanisms. Recent studies indicate that diacylglycer ... Full text Link to item Cite

Diacylglycerol kinase zeta regulates microbial recognition and host resistance to Toxoplasma gondii.

Journal article J Exp Med · April 16, 2007 Mammalian Toll-like receptors (TLRs) recognize microbial pathogen-associated molecular patterns and are critical for innate immunity against microbial infection. Diacylglycerol (DAG) kinases (DGKs) regulate the intracellular levels of two important second ... Full text Link to item Cite

T-B+NK+ severe combined immunodeficiency caused by complete deficiency of the CD3zeta subunit of the T-cell antigen receptor complex.

Journal article Blood · April 15, 2007 CD3zeta is a subunit of the T-cell antigen receptor (TCR) complex required for its assembly and surface expression that also plays an important role in TCR-mediated signal transduction. We report here a patient with T(-)B(+)NK(+) severe combined immunodefi ... Full text Link to item Cite

The role of diacylglycerol kinases in T cell anergy.

Journal article Ernst Schering Found Symp Proc · 2007 Engagement of the T cell antigen receptor (TCR) results in the activation of multiple biochemical second messenger cascades that must be integrated for the appropriate T cell response. Once the critical TCR-stimulated signaling pathway is initiated by acti ... Link to item Cite

Disruption of diacylglycerol metabolism impairs the induction of T cell anergy.

Journal article Nat Immunol · November 2006 Anergic T cells have altered diacylglycerol metabolism, but whether that altered metabolism has a causative function in the induction of T cell anergy is not apparent. To test the importance of diacylglycerol metabolism in T cell anergy, we manipulated dia ... Full text Link to item Cite

Impaired degranulation but enhanced cytokine production after Fc epsilonRI stimulation of diacylglycerol kinase zeta-deficient mast cells.

Journal article J Exp Med · June 12, 2006 Calcium and diacylglycerol are critical second messengers that together effect mast cell degranulation after allergen cross-linking of immunoglobulin (Ig)E-bound FcepsilonRI. Diacylglycerol kinase (DGK)zeta is a negative regulator of diacylglycerol-depende ... Full text Link to item Cite

Transcriptional regulation of Src homology 2 domain-containing leukocyte phosphoprotein of 76 kDa: dissection of key promoter elements.

Journal article J Immunol · December 15, 2003 SLP-76 (Src homology 2 domain-containing leukocyte phosphoprotein of 76 kDa) is an adaptor molecule expressed in all hemopoietic cell lineages except mature B cells and is known to play critical roles in the function of T cells, mast cells, and platelets a ... Full text Link to item Cite

Enhanced T cell responses due to diacylglycerol kinase zeta deficiency.

Journal article Nat Immunol · September 2003 Much is known about how T cell receptor (TCR) engagement leads to T cell activation; however, the mechanisms terminating TCR signaling remain less clear. Diacylglycerol, generated after TCR ligation, is essential in T cells. Its function must be controlled ... Full text Link to item Cite

Regulation of hematopoietic cell development and activation by adapter proteins.

Journal article Immunol Res · 2003 Adapter proteins, molecules with modular domains that mediate intermolecular interactions, play critical roles in the regulation of signaling events in all cell types. A major focus of our laboratory has been to examine the role of adapter molecules in hem ... Full text Link to item Cite

Regulation of T cell receptor-induced activation of the Ras-ERK pathway by diacylglycerol kinase zeta.

Journal article J Biol Chem · August 23, 2002 T cell development in the thymus and activation of mature T cells in the periphery depend on signals stimulated by engagement of the T cell antigen receptor (TCR). Among the second messenger cascades initiated by TCR ligation include the phosphatidylinosit ... Full text Link to item Cite

Assessing a role for enhancer-blocking activity in gene regulation within the murine T-cell receptor alpha/delta locus.

Journal article Immunology · September 2001 Although situated close together within the T-cell receptor (TCR) alpha/delta locus, TCR delta and TCR alpha gene segments are controlled by two developmental stage-specific enhancers and are activated according to distinct developmental programmes. We pre ... Full text Link to item Cite

Accessibility control of T cell receptor gene rearrangement in developing thymocytes. The TCR alpha/delta locus.

Journal article Immunol Res · 2000 The joining of T cell receptor (TCR) and immunoglobulin (Ig) gene segments through the process of V(D)J recombination occurs in a lineage-specific and developmental-stage-specific way during the early stages of lymphocyte development. Such developmental re ... Full text Link to item Cite

Flanking nuclear matrix attachment regions synergize with the T cell receptor delta enhancer to promote V(D)J recombination.

Journal article Proc Natl Acad Sci U S A · October 12, 1999 Previous studies have identified nuclear matrix attachment regions (MARs) that are closely associated with transcriptional enhancers in the IgH, Igkappa, and T cell receptor (TCR) beta loci, but have yielded conflicting information regarding their function ... Full text Link to item Cite

Enhancer-blocking activity within the DNase I hypersensitive site 2 to 6 region between the TCR alpha and Dad1 genes.

Journal article J Immunol · July 1, 1999 Although tightly linked, the TCR alpha and delta genes are expressed specifically in T lymphocytes, whereas the Dad1 gene is ubiquitously expressed. Between TCR alpha and Dad1 are eight DNase I hypersensitive sites (HS). HS1 colocalizes with the TCR alpha ... Link to item Cite

Developmental regulation of V(D)J recombination at the TCR alpha/delta locus.

Journal article Immunol Rev · October 1998 The T-cell receptor (TCR) alpha/delta locus includes a large number of V, D, J and C gene segments that are used to produce functional TCR delta and TCR alpha chains expressed by distinct subsets of T lymphocytes. V(D)J recombination events within the locu ... Full text Link to item Cite

An enhancer-blocking element between alpha and delta gene segments within the human T cell receptor alpha/delta locus.

Journal article Proc Natl Acad Sci U S A · May 13, 1997 T cell receptor (TCR) alpha and delta gene segments are organized within a single genetic locus but are differentially regulated during T cell development. An enhancer-blocking element (BEAD-1, for blocking element alpha/delta 1) was localized to a 2.0-kb ... Full text Link to item Cite

Regulation of T cell receptor delta gene rearrangement by CBF/PEBP2.

Journal article J Exp Med · April 7, 1997 We have analyzed transgenic mice carrying versions of a human T cell receptor (TCR)-delta gene minilocus to study the developmental control of VDJ (variable/diversity/joining) recombination. Previous data indicated that a 1.4-kb DNA fragment carrying the T ... Full text Link to item Cite