Scholars@Duke
Michael Dee Gunn

Michael Dee Gunn

Professor of Medicine
Medicine, Cardiology
michael.gunn@duke.edu
Duke Box 102143, Durham, NC 27710
CARL Building Room 180B, Durham, NC 27703

Selected Publications

Figure 2 from Peripheral Blood IFN Responses to Toll-Like Receptor 1/2 Signaling Associate with Longer Survival in Men with Metastatic Prostate Cancer Treated with Sipuleucel-T

Other · October 18, 2024 <p>Stronger IFN-β responses to TLR1/2 stimulation associates with longer survival after sip-T therapy. <b>A,</b> HRs ± 95% CIs from a Cox proportional hazards model comparing induction of each cytokine (fold mock control) after TL ... Full text Cite

Figure 3 from Peripheral Blood IFN Responses to Toll-Like Receptor 1/2 Signaling Associate with Longer Survival in Men with Metastatic Prostate Cancer Treated with Sipuleucel-T

Other · October 18, 2024 <p>IFN-β induction after TLR1/2 stimulation associates with PBMC ELISpot responses to Fluzone, PHA, and CEFT (cytomegalovirus, EBV, Fluzone, and Tetanus peptide pool). <b>A,</b> ELISpot SFU after each indicated stimulant (<i&gt ... Full text Cite

Figure 1 from Peripheral Blood IFN Responses to Toll-Like Receptor 1/2 Signaling Associate with Longer Survival in Men with Metastatic Prostate Cancer Treated with Sipuleucel-T

Other · October 18, 2024 <p>Study design and <i>in vitro</i> responsiveness of PBMCs from patients with mCRPC to PRR agonist prior to sip-T treatment. <b>A,</b> Banked pretreatment PBMCs from the PRIME sip-T discovery cohort (<i>n</i& ... Full text Cite

Figure 5 from Peripheral Blood IFN Responses to Toll-Like Receptor 1/2 Signaling Associate with Longer Survival in Men with Metastatic Prostate Cancer Treated with Sipuleucel-T

Other · October 18, 2024 <p>TLR1/2 responses associate with post–sip-T survival independent of race and TLR1/2 SNP status. <b>A–C,</b> Survival stratified by race in the merged PRIME and KCI cohorts (<b>A</b>), PRIME cohort alone (<b>B&l ... Full text Cite

Data from Peripheral Blood IFN Responses to Toll-Like Receptor 1/2 Signaling Associate with Longer Survival in Men with Metastatic Prostate Cancer Treated with Sipuleucel-T

Other · October 18, 2024 <div>Abstract<p>Mounting evidence links systemic innate immunity with cancer immune surveillance. In advanced metastatic castration-resistant prostate cancer (mCRPC), Black patients have been found to have increased inflammatory markers ... Full text Cite

Figure 4 from Peripheral Blood IFN Responses to Toll-Like Receptor 1/2 Signaling Associate with Longer Survival in Men with Metastatic Prostate Cancer Treated with Sipuleucel-T

Other · October 18, 2024 <p>Black race and TLR1-602I SNP associate with stronger responses to TLR1/2 stimulation. <b>A,</b> Supernatant cytokine release separated by Black (<i>n</i> = 15) vs. White (<i>n</i> = 91) for each stimulat ... Full text Cite

Peripheral Blood IFN Responses to Toll-Like Receptor 1/2 Signaling Associate with Longer Survival in Men with Metastatic Prostate Cancer Treated with Sipuleucel-T.

Journal Article Cancer Res Commun · October 1, 2024 UNLABELLED: Mounting evidence links systemic innate immunity with cancer immune surveillance. In advanced metastatic castration-resistant prostate cancer (mCRPC), Black patients have been found to have increased inflammatory markers and longer survival aft ... Full text Link to item Cite

Recapitulation of human pathophysiology and identification of forensic biomarkers in a translational model of chlorine inhalation injury.

Journal Article Am J Physiol Lung Cell Mol Physiol · April 1, 2024 Chlorine gas (Cl2) has been repeatedly used as a chemical weapon, first in World War I and most recently in Syria. Life-threatening Cl2 exposures frequently occur in domestic and occupational environments, and in transportation accidents. Modeling the huma ... Full text Link to item Cite

Altered ontogeny and transcriptomic signatures of tissue-resident pulmonary interstitial macrophages ameliorate allergic airway hyperresponsiveness.

Journal Article Front Immunol · 2024 INTRODUCTION: Environmental exposures and experimental manipulations can alter the ontogenetic composition of tissue-resident macrophages. However, the impact of these alterations on subsequent immune responses, particularly in allergic airway diseases, re ... Full text Link to item Cite

Antigen-loaded Monocyte Administration and Flt3 Ligand Augment the Antitumor Efficacy of Immune Checkpoint Blockade in a Murine Melanoma Model.

Journal Article J Immunother · November 2023 Undifferentiated monocytes can be loaded with tumor antigens (Ag) and administered intravenously to induce antitumor cytotoxic T lymphocyte (CTL) responses. This vaccination strategy exploits an endogenous Ag cross-presentation pathway, where Ag-loaded mon ... Full text Link to item Cite

CD8+ T cells maintain killing of MHC-I-negative tumor cells through the NKG2D-NKG2DL axis.

Journal Article Nat Cancer · September 2023 The accepted paradigm for both cellular and anti-tumor immunity relies upon tumor cell killing by CD8+ T cells recognizing cognate antigens presented in the context of target cell major histocompatibility complex (MHC) class I (MHC-I) molecules. Likewise, ... Full text Link to item Cite

Antigen loaded monocytes prime CD4+ T cell responses through Notch2 dependent cDC2

Conference The Journal of Immunology · May 1, 2023 AbstractCellular vaccines, primarily monocyte-derived dendritic cells (MoDC), have recently been realized as therapeutic cancer vaccines with modest clinical efficacy. Understanding the mechanism by which th ... Full text Cite

Immunotoxin-αCD40 therapy activates innate and adaptive immunity and generates a durable antitumor response in glioblastoma models.

Journal Article Sci Transl Med · February 8, 2023 D2C7-immunotoxin (IT), a dual-specific IT targeting wild-type epidermal growth factor receptor (EGFR) and mutant EGFR variant III (EGFRvIII) proteins, demonstrates encouraging survival outcomes in a subset of patients with glioblastoma. We hypothesized tha ... Full text Link to item Cite

Lessons from the pandemic: Responding to emerging zoonotic viral diseases-a Keystone Symposia report.

Journal Article Annals of the New York Academy of Sciences · December 2022 The COVID-19 pandemic caught the world largely unprepared, including scientific and policy communities. On April 10-13, 2022, researchers across academia, industry, government, and nonprofit organizations met at the Keystone symposium "Lessons from the Pan ... Full text Open Access Cite

Nicotinic stimulation of splenic T cells is protective in endoscopic retrograde cholangiopancreatography-induced acute pancreatitis in mice.

Journal Article Am J Physiol Gastrointest Liver Physiol · November 1, 2022 It has previously been shown that current smoking is protective against endoscopic retrograde cholangiopancreatography (ERCP)-induced acute pancreatitis, but the mechanism of this effect was not identified. We tested the hypothesis that nicotine is the act ... Full text Link to item Cite

Neuronal CaMKK2 promotes immunosuppression and checkpoint blockade resistance in glioblastoma.

Journal Article Nat Commun · October 29, 2022 Glioblastoma (GBM) is notorious for its immunosuppressive tumor microenvironment (TME) and is refractory to immune checkpoint blockade (ICB). Here, we identify calmodulin-dependent kinase kinase 2 (CaMKK2) as a driver of ICB resistance. CaMKK2 is highly ex ... Full text Link to item Cite

Monocytes as a Cellular Vaccine Platform to Induce Antitumor Immunity.

Journal Article Methods Mol Biol · 2022 We recently developed a monocyte-based cellular vaccine platform for cancer treatment. In contrast to the traditional utilization of monocytes as precursors to generate dendritic cells (DC) for vaccination purposes, we find that freshly isolated monocytes ... Full text Link to item Cite

Broad immunophenotyping of the murine brain tumor microenvironment.

Journal Article J Immunol Methods · December 2021 Here we present a 14-color flow cytometry panel for the evaluation of 13 myeloid and lymphoid populations within murine glioblastoma samples. Reagents, processing protocols, and downstream analyses were thoroughly validated and optimized to resolve the fol ... Full text Link to item Cite

Ultrasensitive point-of-care immunoassay for secreted glycoprotein detects Ebola infection earlier than PCR.

Journal Article Sci Transl Med · April 7, 2021 Ebola virus (EBOV) hemorrhagic fever outbreaks have been challenging to deter due to the lack of health care infrastructure in disease-endemic countries and a corresponding inability to diagnose and contain the disease at an early stage. EBOV vaccines and ... Full text Link to item Cite

Th17 Immunity in the Colon Is Controlled by Two Novel Subsets of Colon-Specific Mononuclear Phagocytes.

Conference Front Immunol · 2021 Intestinal immunity is coordinated by specialized mononuclear phagocyte populations, constituted by a diversity of cell subsets. Although the cell subsets constituting the mononuclear phagocyte network are thought to be similar in both small and large inte ... Full text Link to item Cite

Nonclassical Monocytes Sense Hypoxia, Regulate Pulmonary Vascular Remodeling, and Promote Pulmonary Hypertension.

Journal Article J Immunol · March 15, 2020 Featured Publication An increasing body of evidence suggests that bone marrow-derived myeloid cells play a critical role in the pathophysiology of pulmonary hypertension (PH). However, the true requirement for myeloid cells in PH development has not been demonstrated, and a sp ... Full text Link to item Cite

Antigen-loaded monocyte administration induces potent therapeutic antitumor T cell responses.

Journal Article J Clin Invest · February 3, 2020 Featured Publication Efficacy of dendritic cell (DC) cancer vaccines is classically thought to depend on their antigen-presenting cell (APC) activity. Studies show, however, that DC vaccine priming of cytotoxic T lymphocytes (CTLs) requires the activity of endogenous DCs, sugg ... Full text Link to item Cite

Brain immunology and immunotherapy in brain tumours.

Journal Article Nat Rev Cancer · January 2020 Featured Publication Gliomas, the most common malignant primary brain tumours, remain universally lethal. Yet, seminal discoveries in the past 5 years have clarified the anatomy, genetics and function of the immune system within the central nervous system (CNS) and altered the ... Full text Link to item Cite

Twist1 in Infiltrating Macrophages Attenuates Kidney Fibrosis via Matrix Metallopeptidase 13-Mediated Matrix Degradation.

Journal Article J Am Soc Nephrol · September 2019 BACKGROUND: Following an acute insult, macrophages regulate renal fibrogenesis through the release of various factors that either encourage the synthesis of extracellular matrix synthesis or the degradation of matrix via endocytosis, proteolysis, or both. ... Full text Link to item Cite

Improved efficacy against malignant brain tumors with EGFRwt/EGFRvIII targeting immunotoxin and checkpoint inhibitor combinations.

Journal Article J Immunother Cancer · May 29, 2019 BACKGROUND: D2C7-IT is a novel immunotoxin (IT) targeting wild-type epidermal growth factor receptor (EGFRwt) and mutant EGFR variant III (EGFRvIII) proteins in glioblastoma. In addition to inherent tumoricidal activity, immunotoxins induce secondary immun ... Full text Open Access Link to item Cite

Removal of microglial-specific MyD88 signaling alters dentate gyrus doublecortin and enhances opioid addiction-like behaviors.

Journal Article Brain Behav Immun · February 2019 Drugs of abuse promote a potent immune response in central nervous system (CNS) via the activation of microglia and astrocytes. However, the molecular mechanisms underlying microglial activation during addiction are not well known. We developed and functio ... Full text Link to item Cite

Biased agonists of the chemokine receptor CXCR3 differentially control chemotaxis and inflammation.

Journal Article Sci Signal · November 6, 2018 The chemokine receptor CXCR3 plays a central role in inflammation by mediating effector/memory T cell migration in various diseases; however, drugs targeting CXCR3 and other chemokine receptors are largely ineffective in treating inflammation. Chemokines, ... Full text Link to item Cite

Interleukin 1 receptor (IL-1R1) activation exacerbates toxin-induced acute kidney injury.

Journal Article Am J Physiol Renal Physiol · September 1, 2018 Acute kidney injury (AKI) is a leading cause of morbidity and mortality. Drug-induced/toxic AKI can be caused by a number of therapeutic agents. Cisplatin is an effective chemotherapeutic agent whose administration is limited by significant nephrotoxicity. ... Full text Link to item Cite

Sequestration of T cells in bone marrow in the setting of glioblastoma and other intracranial tumors.

Journal Article Nat Med · September 2018 T cell dysfunction contributes to tumor immune escape in patients with cancer and is particularly severe amidst glioblastoma (GBM). Among other defects, T cell lymphopenia is characteristic, yet often attributed to treatment. We reveal that even treatment- ... Full text Link to item Cite

Myoepithelial Cells of Submucosal Glands Can Function as Reserve Stem Cells to Regenerate Airways after Injury.

Journal Article Cell Stem Cell · May 3, 2018 Cells demonstrate plasticity following injury, but the extent of this phenomenon and the cellular mechanisms involved remain underexplored. Using single-cell RNA sequencing (scRNA-seq) and lineage tracing, we uncover that myoepithelial cells (MECs) of the ... Full text Link to item Cite

Nanoparticle formulation improves doxorubicin efficacy by enhancing host antitumor immunity.

Journal Article J Control Release · January 10, 2018 Strategies that enhance the host antitumor immune response promise to revolutionize cancer therapy. Optimally mobilizing the immune system will likely require a multi-pronged approach to overcome the resistance developed by tumors to therapy. Recently, it ... Full text Link to item Cite

The cholesterol metabolite 27 hydroxycholesterol facilitates breast cancer metastasis through its actions on immune cells.

Journal Article Nat Commun · October 11, 2017 Obesity and elevated circulating cholesterol are risk factors for breast cancer recurrence, while the use of statins, cholesterol biosynthesis inhibitors widely used for treating hypercholesterolemia, is associated with improved disease-free survival. Here ... Full text Link to item Cite

C-C Motif Chemokine 5 Attenuates Angiotensin II-Dependent Kidney Injury by Limiting Renal Macrophage Infiltration.

Journal Article Am J Pathol · November 2016 Inappropriate activation of the renin angiotensin system (RAS) is a key contributor to the pathogenesis of essential hypertension. During RAS activation, infiltration of immune cells into the kidney exacerbates hypertension and renal injury. However, the m ... Full text Open Access Link to item Cite

Organizing pneumonia in mice and men.

Journal Article J Transl Med · June 10, 2016 BACKGROUND: Organizing pneumonia is a reaction pattern and an inflammatory response to acute lung injuries, and is characterized by intraluminal plugs of granulation tissue in distal airspaces. In contrast to other fibrotic pulmonary diseases, organizing p ... Full text Link to item Cite

Flow Cytometric Analysis of Myeloid Cells in Human Blood, Bronchoalveolar Lavage, and Lung Tissues.

Journal Article Am J Respir Cell Mol Biol · January 2016 Clear identification of specific cell populations by flow cytometry is important to understand functional roles. A well-defined flow cytometry panel for myeloid cells in human bronchoalveolar lavage (BAL) and lung tissue is currently lacking. The objective ... Full text Link to item Cite

A Protocol for the Comprehensive Flow Cytometric Analysis of Immune Cells in Normal and Inflamed Murine Non-Lymphoid Tissues.

Journal Article PLoS One · 2016 Featured Publication Flow cytometry is used extensively to examine immune cells in non-lymphoid tissues. However, a method of flow cytometric analysis that is both comprehensive and widely applicable has not been described. We developed a protocol for the flow cytometric analy ... Full text Open Access Link to item Cite

Arginine deprivation and immune suppression in a mouse model of Alzheimer's disease.

Journal Article J Neurosci · April 15, 2015 Featured Publication The pathogenesis of Alzheimer's disease (AD) is a critical unsolved question; and although recent studies have demonstrated a strong association between altered brain immune responses and disease progression, the mechanistic cause of neuronal dysfunction a ... Full text Link to item Cite

Tetanus toxoid and CCL3 improve dendritic cell vaccines in mice and glioblastoma patients.

Journal Article Nature · March 19, 2015 Featured Publication After stimulation, dendritic cells (DCs) mature and migrate to draining lymph nodes to induce immune responses. As such, autologous DCs generated ex vivo have been pulsed with tumour antigens and injected back into patients as immunotherapy. While DC vacci ... Full text Open Access Link to item Cite

Flow Cytometry Of Human Bronchoalveolar Lavage Fluid And Lung Tissue Identifies Interstitial Macrophages

Conference AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE · January 1, 2015 Link to item Cite

Role of C-C motif ligand 2 and C-C motif receptor 2 in murine pulmonary graft-versus-host disease after lipopolysaccharide inhalations.

Journal Article Am J Respir Cell Mol Biol · December 2014 Environmental exposures are a potential trigger of chronic pulmonary graft-versus-host disease (pGVHD) after successful recovery from hematopoietic cell transplant (HCT). We hypothesized that inhalations of LPS, a prototypic environmental stimulus, trigger ... Full text Link to item Cite

S1P-Dependent trafficking of intracellular yersinia pestis through lymph nodes establishes Buboes and systemic infection.

Journal Article Immunity · September 18, 2014 Pathologically swollen lymph nodes (LNs), or buboes, characterize Yersinia pestis infection, yet how they form and function is unknown. We report that colonization of the draining LN (dLN) occurred due to trafficking of infected dendritic cells and monocyt ... Full text Link to item Cite

RANDOMIZATION OF PATIENTS WITH GLIOBLASTOMA TO VACCINE SITE PRE-CONDITIONING WITH TETANUS-DIPHTHERIA TOXOID SYSTEMICALLY ENHANCES MIGRATION AND THERAPEUTIC EFFECT OF CYTOMEGALOVIRUS PP65-PULSED DENDRITIC CELL VACCINE IN A MIP-1α-DEPENDENT FASHION.

Conference Neuro Oncol · July 2014 Dendritic cell (DC) vaccine efficacy is limited by suboptimal migration to vaccine site-draining lymph nodes (VDLNs). In mice, vaccine site conditioning with inflammatory cytokines or mature DCs increases DC trafficking and the induction of antigen-specifi ... Full text Link to item Cite

Loss of basal cells precedes bronchiolitis obliterans-like pathological changes in a murine model of chlorine gas inhalation.

Journal Article Am J Respir Cell Mol Biol · November 2013 Featured Publication Bronchiolitis obliterans (BO) is a major cause of chronic airway dysfunction after toxic chemical inhalation. The pathophysiology of BO is not well understood, but epithelial cell injury has been closely associated with the development of fibrotic lesions ... Full text Link to item Cite

Identification of a tissue-specific, C/EBPβ-dependent pathway of differentiation for murine peritoneal macrophages.

Journal Article J Immunol · November 1, 2013 Macrophages and dendritic cells (DC) are distributed throughout the body and play important roles in pathogen detection and tissue homeostasis. In tissues, resident macrophages exhibit distinct phenotypes and activities, yet the transcriptional pathways th ... Full text Link to item Cite

CCR2 deficiency, dysregulation of Notch signaling, and spontaneous pulmonary arterial hypertension.

Journal Article Am J Respir Cell Mol Biol · May 2013 In pulmonary arterial hypertension (PAH), there is overexpression of the chemokine, C-C chemokine ligand type 2 (CCL2), and infiltration of myeloid cells into the pulmonary vasculature. Inhibition of CCL2 in animals decreases PAH, suggesting that the CCL2 ... Full text Link to item Cite

A comparison of non-toxin vaccine adjuvants for their ability to enhance the immunogenicity of nasally-administered anthrax recombinant protective antigen.

Journal Article Vaccine · March 1, 2013 Development of nasal immunization for human use is hindered by the lack of acceptable adjuvants. Although CT is an effective adjuvant, its toxicity will likely prevent its use in nasal vaccines. This study compared non-toxin adjuvants to CT for their abili ... Full text Link to item Cite

Natural genetic variation of integrin alpha L (Itgal) modulates ischemic brain injury in stroke.

Journal Article PLoS Genet · 2013 During ischemic stroke, occlusion of the cerebrovasculature causes neuronal cell death (infarction), but naturally occurring genetic factors modulating infarction have been difficult to identify in human populations. In a surgically induced mouse model of ... Full text Open Access Link to item Cite

NLRP3 inflammasome induces chemotactic immune cell migration to the CNS in experimental autoimmune encephalomyelitis.

Journal Article Proc Natl Acad Sci U S A · June 26, 2012 The NLRP3 inflammasome is a multiprotein complex consisting of three kinds of proteins, NLRP3, ASC, and pro-caspase-1, and plays a role in sensing pathogens and danger signals in the innate immune system. The NLRP3 inflammasome is thought to be involved in ... Full text Link to item Cite

A macrophage subpopulation recruited by CC chemokine ligand-2 clears apoptotic cells in noninfectious lung injury.

Journal Article Am J Physiol Lung Cell Mol Physiol · May 1, 2012 Featured Publication CC chemokine ligand-2 (CCL2)/monocyte chemoattractant protein (MCP)-1 expression is upregulated during pulmonary inflammation, and the CCL2-CCR2 axis plays a critical role in leukocyte recruitment and promotion of host defense against infection. The role o ... Full text Link to item Cite

Maximal adjuvant activity of nasally delivered IL-1α requires adjuvant-responsive CD11c(+) cells and does not correlate with adjuvant-induced in vivo cytokine production.

Journal Article J Immunol · March 15, 2012 IL-1 has been shown to have strong mucosal adjuvant activities, but little is known about its mechanism of action. We vaccinated IL-1R1 bone marrow (BM) chimeric mice to determine whether IL-1R1 expression on stromal cells or hematopoietic cells was suffic ... Full text Link to item Cite

Ozone inhalation promotes CX3CR1-dependent maturation of resident lung macrophages that limit oxidative stress and inflammation.

Journal Article J Immunol · November 1, 2011 Inhalation of ambient ozone alters populations of lung macrophages. However, the impact of altered lung macrophage populations on the pathobiology of ozone is poorly understood. We hypothesized that subpopulations of macrophages modulate the response to oz ... Full text Link to item Cite

Recruited exudative macrophages selectively produce CXCL10 after noninfectious lung injury.

Journal Article Am J Respir Cell Mol Biol · October 2011 The chemokine, CXCL10, and its cognate receptor, CXCR3, are important mediators of the pathobiology of lung fibrosis. Macrophages are a known source of CXCL10, but their specific source in the lung is poorly defined due to incomplete characterization of ma ... Full text Link to item Cite

Activation of metabotropic glutamate receptor 7 in spinal cord inhibits pain and hyperalgesia in a novel formalin model in sheep.

Journal Article Behav Pharmacol · September 2011 This study set out to characterize the contribution of group III metabotropic glutamate receptor 7 activation to nociceptive behaviour and mechanical hypersensitivity in a novel formalin test in sheep. The mGlu receptor 7 allosteric agonist, N,N'-dibenzhyd ... Full text Link to item Cite

Cowpox virus induces interleukin-10 both in vitro and in vivo.

Journal Article Virology · August 15, 2011 Cowpox virus infection induces interleukin-10 (IL-10) production from mouse bone marrow-derived dendritic cells (BMDCs) or cells of the mouse macrophage line (RAW264.7) at about 1800 pg/ml, whereas infections with vaccinia virus (strains WR or MVA) induced ... Full text Link to item Cite

NUR who? An orphan transcription factor holds promise for monomaniacs.

Journal Article Nat Immunol · July 19, 2011 Featured Publication Full text Link to item Cite

CCR2-antagonist prophylaxis reduces pulmonary immune pathology and markedly improves survival during influenza infection.

Journal Article J Immunol · January 1, 2011 Featured Publication Infection with influenza virus induces severe pulmonary immune pathology that leads to substantial human mortality. Although antiviral therapy is effective in preventing infection, no current therapy can prevent or treat influenza-induced lung injury. Prev ... Full text Link to item Cite

Mast cells augment adaptive immunity by orchestrating dendritic cell trafficking through infected tissues.

Journal Article Cell Host Microbe · October 22, 2009 Mast cells (MCs) are best known for eliciting harmful reactions, mostly after primary immunity has been established. Here, we report that, during footpad infection with E. coli in MC-deficient mice, as compared to their MC-sufficient counterparts, the seru ... Full text Link to item Cite

The selective metabotropic glutamate receptor 7 allosteric agonist AMN082 inhibits inflammatory pain-induced and incision-induced hypersensitivity in rat.

Journal Article Behav Pharmacol · October 2009 This study characterized the contribution of metabotropic glutamate receptor 7 (mGlu7 receptor) activation to the development of inflammatory hyperalgesia and allodynia, using a novel, systemically active mGlu7 receptor allosteric agonist, N, N'-dibenzhydr ... Full text Link to item Cite

Blood-derived inflammatory dendritic cells in lymph nodes stimulate acute T helper type 1 immune responses.

Journal Article Nat Immunol · April 2009 Featured Publication T helper type 1 (T(H)1)-polarized immune responses, which confer protection against intracellular pathogens, are thought to be initiated by dendritic cells (DCs) that enter lymph nodes from peripheral tissues. Here we found after viral infection or immuniz ... Full text Link to item Cite

Identification of recombinant antibodies against multiple distinct toll-like receptors by homolog mining a single immune scFv phage library.

Journal Article J Immunol Methods · January 30, 2009 Featured Publication The generation of recombinant single-chain antibodies from either non-immune or immune phage display antibody libraries is an effective means to obtain high affinity antibodies against a specific target. Non-immune libraries contain a wide variety of antib ... Full text Link to item Cite

Arginase-1 Expression in CXCR3 Knockout Mice Identifies Alternatively Activated Macrophages after Non-Infectious Lung Injury

Journal Article AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE · January 1, 2009 Link to item Cite

Mice that overexpress CC chemokine ligand 2 in their lungs show increased protective immunity to infection with Mycobacterium bovis bacille Calmette-Guérin.

Journal Article J Infect Dis · October 1, 2008 BACKGROUND: The acute phase of mycobacterial lung infection is characterized by a nearly exponential outgrowth of mycobacteria in the alveolar airspace and lung parenchymal tissue, suggesting insufficient early protective immunity against mycobacterial cha ... Full text Link to item Cite

An entirely cell-based system to generate single-chain antibodies against cell surface receptors.

Journal Article J Mol Biol · May 30, 2008 Featured Publication The generation of recombinant antibodies (Abs) using phage display is a proven method to obtain a large variety of Abs that bind with high affinity to a given antigen. Traditionally, the generation of single-chain Abs depends on the use of recombinant prot ... Full text Link to item Cite

Autotaxin, an ectoenzyme that produces lysophosphatidic acid, promotes the entry of lymphocytes into secondary lymphoid organs.

Journal Article Nat Immunol · April 2008 The extracellular lysophospholipase D autotaxin (ATX) and its product, lysophosphatidic acid, have diverse functions in development and cancer, but little is known about their functions in the immune system. Here we found that ATX had high expression in th ... Full text Link to item Cite

CCR2+ monocyte-derived dendritic cells and exudate macrophages produce influenza-induced pulmonary immune pathology and mortality.

Journal Article J Immunol · February 15, 2008 Featured Publication Infection with pathogenic influenza virus induces severe pulmonary immune pathology, but the specific cell types that cause this have not been determined. We characterized inflammatory cell types in mice that overexpress MCP-1 (CCL2) in the lungs, then exa ... Full text Link to item Cite

Lung-specific overexpression of CC chemokine ligand (CCL) 2 enhances the host defense to Streptococcus pneumoniae infection in mice: role of the CCL2-CCR2 axis.

Journal Article J Immunol · May 1, 2007 Mononuclear phagocytes are critical components of the innate host defense of the lung to inhaled bacterial pathogens. The monocyte chemotactic protein CCL2 plays a pivotal role in inflammatory mononuclear phagocyte recruitment. In this study, we tested the ... Full text Link to item Cite

Enhanced allergen-induced airway inflammation in paucity of lymph node T cell (plt) mutant mice.

Journal Article J Allergy Clin Immunol · December 2006 BACKGROUND: Dendritic cells and lymphocytes play a central role in allergic asthma. Chemokines for these cells include the CCR7 agonists secondary lymphoid chemokine/CCL21 and EBV-induced lymphoid chemokine/CCL19, but their role in allergic asthma is poorl ... Full text Link to item Cite

TLR4 signaling attenuates ongoing allergic inflammation.

Journal Article J Immunol · May 15, 2006 The relationship between LPS exposure and allergic asthma is poorly understood. Epidemiologic studies in humans have found that exposure to LPS can protect, have no effect, or exacerbate allergic asthma. Similarly, LPS has had variable effects on allergic ... Full text Link to item Cite

Permanent survival of fully MHC-mismatched islet allografts by targeting a single chemokine receptor pathway.

Journal Article J Immunol · November 15, 2005 Chemokine receptor blockade can diminish the recruitment of host effector cells and prolong allograft survival, but little is known of the role of chemokine receptors in promoting host sensitization. We engrafted fully allogeneic islets into streptozotocin ... Full text Link to item Cite

PF4/heparin complexes are T cell-dependent antigens.

Journal Article Blood · August 1, 2005 Heparin-induced thrombocytopenia (HIT) is a life-threatening, thrombotic disorder associated with development of anti-platelet factor 4 (anti-PF4)/heparin autoantibodies. Little is known about the antigenic and cellular requirements that initiate the immun ... Full text Link to item Cite

The critical role of hematopoietic cells in lipopolysaccharide-induced airway inflammation.

Journal Article Am J Respir Crit Care Med · April 15, 2005 Rapid and selective recruitment of neutrophils into the airspace in response to LPS facilitates the clearance of bacterial pathogens. However, neutrophil infiltration can also participate in the development and progression of environmental airway disease. ... Full text Link to item Cite

Should we B-leavin' now?

Journal Article Nat Immunol · July 2004 Full text Link to item Cite

A CD91-positive subset of CD11c+ blood dendritic cells: characterization of the APC that functions to enhance adaptive immune responses against CD91-targeted antigens.

Journal Article J Immunol · January 1, 2004 Dendritic cells (DC) and other APCs rely on a number of specialized receptors to facilitate the uptake and intracellular accumulation of Ags. In this capacity, APCs use receptor-mediated endocytosis to enhance Ag presentation and the stimulation of Ag-spec ... Full text Link to item Cite

Mast cell-derived tumor necrosis factor induces hypertrophy of draining lymph nodes during infection.

Journal Article Nat Immunol · December 2003 Palpable swelling of regional lymph nodes is a common sequela of microbial infections but the mechanism responsible for the sequestration and subsequent coordination of lymphocyte responses within these dynamic structures remains poorly understood. Here we ... Full text Link to item Cite

Chemokine mediated control of dendritic cell migration and function.

Journal Article Semin Immunol · October 2003 Dendritic cells (DC) have historically been viewed as a group of functionally homogeneous cell types that act to stimulate Ag-specific immune responses after migrating to secondary lymphoid organs. DC patterns of chemokine responsiveness have generally bee ... Full text Link to item Cite

FTY720 stimulates multidrug transporter- and cysteinyl leukotriene-dependent T cell chemotaxis to lymph nodes.

Journal Article J Clin Invest · March 2003 FTY720 is a sphingosine-derived immunosuppressant. Phosphorylated FTY720 promotes T cell homing from spleen and peripheral blood to LNs by acting as an agonist for sphingosine-1-phosphate (S1P) receptors. Here we demonstrate that FTY720 enhances the activi ... Full text Link to item Cite

An essential role for Prox1 in the induction of the lymphatic endothelial cell phenotype.

Journal Article EMBO J · April 2, 2002 The process of angiogenesis has been well documented, but little is known about the biology of lymphatic endothelial cells and the molecular mechanisms controlling lymphangiogenesis. The homeobox gene Prox1 is expressed in a subpopulation of endothelial ce ... Full text Link to item Cite

Chemokine ligand and receptor expression in the pregnant uterus: reciprocal patterns in complementary cell subsets suggest functional roles.

Journal Article Am J Pathol · December 2001 During human pregnancy, the uterus is infiltrated by a population of maternal leukocytes that co-exist with fetal cytotrophoblasts occupying the decidua and uterine blood vessels. These immune cells, termed "decidual granulated leukocytes," are composed pr ... Full text Link to item Cite

CD11c(+)B220(+)Gr-1(+) cells in mouse lymph nodes and spleen display characteristics of plasmacytoid dendritic cells.

Journal Article J Exp Med · October 15, 2001 Featured Publication Human plasmacytoid dendritic cells (pDCs) are major producers of IFNalpha, are activated by CpG motifs, and are believed to enter lymph nodes (LNs) via L-selectin dependent extravasation across high endothelial venules. To identify a similar murine DC type ... Full text Link to item Cite

Human placental cytotrophoblasts attract monocytes and CD56(bright) natural killer cells via the actions of monocyte inflammatory protein 1alpha.

Journal Article J Exp Med · May 21, 2001 During human pregnancy, the specialized epithelial cells of the placenta (cytotrophoblasts) come into direct contact with immune cells in several locations. In the fetal compartment of the placenta, cytotrophoblast stem cells lie adjacent to macrophages (H ... Full text Link to item Cite

Mice lacking expression of the chemokines CCL21-ser and CCL19 (plt mice) demonstrate delayed but enhanced T cell immune responses.

Journal Article J Exp Med · January 15, 2001 Featured Publication The paucity of lymph node T cells (plt) mutation leads to a loss of CCL21 and CCL19 expression in secondary lymphoid organs. plt mice have defects in the migration of naive T cells and activated dendritic cells into the T cell zones of lymphoid organs, sug ... Full text Link to item Cite

Gene duplications at the chemokine locus on mouse chromosome 4: multiple strain-specific haplotypes and the deletion of secondary lymphoid-organ chemokine and EBI-1 ligand chemokine genes in the plt mutation.

Journal Article J Immunol · January 1, 2001 The murine paucity of lymph node T cell (plt) mutation leads to abnormalities in leukocyte migration and immune response. The causative defect is thought to be a loss of secondary lymphoid-organ chemokine (SLC) expression in lymphoid tissues. We now find t ... Full text Link to item Cite

Cutting edge: hierarchy of chemokine receptor and TCR signals regulating T cell migration and proliferation.

Journal Article J Immunol · July 1, 2000 Chemokines play an important role in establishing the distribution of lymphocyte subpopulations in primary and secondary lymphoid tissues and in the recruitment of leukocytes to sites of inflammation. However, the potential of chemokines to down-regulate i ... Full text Link to item Cite

The CC chemokine thymus-derived chemotactic agent 4 (TCA-4, secondary lymphoid tissue chemokine, 6Ckine, exodus-2) triggers lymphocyte function-associated antigen 1-mediated arrest of rolling T lymphocytes in peripheral lymph node high endothelial venules.

Journal Article J Exp Med · January 3, 2000 T cell homing to peripheral lymph nodes (PLNs) is defined by a multistep sequence of interactions between lymphocytes and endothelial cells in high endothelial venules (HEVs). After initial tethering and rolling via L-selectin, firm adhesion of T cells req ... Full text Link to item Cite

Sulfotransferases of two specificities function in the reconstitution of high endothelial cell ligands for L-selectin.

Journal Article J Cell Biol · May 17, 1999 L-selectin, a lectin-like receptor, mediates rolling of lymphocytes on high endothelial venules (HEVs) in secondary lymphoid organs by interacting with HEV ligands. These ligands consist of a complex of sialomucins, candidates for which are glycosylation- ... Full text Link to item Cite

Mice lacking expression of secondary lymphoid organ chemokine have defects in lymphocyte homing and dendritic cell localization.

Journal Article J Exp Med · February 1, 1999 Featured Publication Secondary lymphoid organ chemokine (SLC) is expressed in high endothelial venules and in T cell zones of spleen and lymph nodes (LNs) and strongly attracts naive T cells. In mice homozygous for the paucity of lymph node T cell (plt) mutation, naive T cells ... Full text Link to item Cite

Lymphotoxin alpha/beta and tumor necrosis factor are required for stromal cell expression of homing chemokines in B and T cell areas of the spleen.

Journal Article J Exp Med · January 18, 1999 Mice deficient in the cytokines tumor necrosis factor (TNF) or lymphotoxin (LT) alpha/beta lack polarized B cell follicles in the spleen. Deficiency in CXC chemokine receptor 5 (CXCR5), a receptor for B lymphocyte chemoattractant (BLC), also causes loss of ... Full text Link to item Cite

Chemokines and B-cell homing to follicles.

Journal Article Curr Top Microbiol Immunol · 1999 Full text Link to item Cite

A high endothelial cell-derived chemokine induces rapid, efficient, and subset-selective arrest of rolling T lymphocytes on a reconstituted endothelial substrate.

Journal Article J Immunol · December 1, 1998 The homing of lymphocytes to secondary lymphoid organs is thought to involve the action of chemokines. Secondary lymphoid-tissue chemokine (SLC), a high endothelial venule (HEV)-associated chemokine, has emerged as a candidate for participating in this pro ... Link to item Cite

Secondary lymphoid-tissue chemokine (SLC) stimulates integrin alpha 4 beta 7-mediated adhesion of lymphocytes to mucosal addressin cell adhesion molecule-1 (MAdCAM-1) under flow.

Journal Article J Immunol · July 15, 1998 The attachment of leukocytes to the endothelium is a multistep process that depends upon a very rapid increase in the adhesive activity of leukocyte integrins. A pertussis toxin-sensitive pathway stimulates integrin-dependent lymphocyte adhesion to Peyer's ... Link to item Cite

Genes for apolipoprotein B and microsomal triglyceride transfer protein are expressed in the heart: evidence that the heart has the capacity to synthesize and secrete lipoproteins.

Journal Article Circulation · July 7, 1998 BACKGROUND: Expression of both the apolipoprotein B (apoB) gene and the microsomal triglyceride transfer protein (MTP) gene is required for the assembly and secretion of triglyceride-rich lipoproteins in the liver and intestine. Both genes have been assume ... Full text Link to item Cite

A B-cell-homing chemokine made in lymphoid follicles activates Burkitt's lymphoma receptor-1.

Journal Article Nature · February 19, 1998 Featured Publication Secondary lymphoid organs (spleen, lymph nodes and Peyer's patches) are divided into compartments, such as B-cell zones (follicles) and T-cell zones, which provide specialized environments for specific steps of the immune response. Migration of lymphocyte ... Full text Link to item Cite

A chemokine expressed in lymphoid high endothelial venules promotes the adhesion and chemotaxis of naive T lymphocytes.

Journal Article Proc Natl Acad Sci U S A · January 6, 1998 Featured Publication Preferential homing of naive lymphocytes to secondary lymphoid organs is thought to involve the action of chemokines, yet no chemokine has been shown to have either the expression pattern or the activities required to mediate this process. Here we show tha ... Full text Link to item Cite

Human apolipoprotein B transgenic mice generated with 207- and 145-kilobase pair bacterial artificial chromosomes. Evidence that a distant 5'-element confers appropriate transgene expression in the intestine.

Journal Article J Biol Chem · November 21, 1997 We reported previously that approximately 80-kilobase pair (kb) P1 bacteriophage clones spanning either the human or mouse apoB gene (clones p158 and p649, respectively) confer apoB expression in the liver of transgenic mice, but not in the intestine. We h ... Full text Link to item Cite

Tissue expression studies on the mouse acyl-CoA: cholesterol acyltransferase gene (Acact): findings supporting the existence of multiple cholesterol esterification enzymes in mice.

Journal Article J Lipid Res · September 1997 Cholesterol esterification is involved in the regulation of cellular cholesterol content and has been hypothesized to play a role in important physiologic processes including intestinal cholesterol absorption, hepatic lipoprotein production, and macrophage ... Link to item Cite

Monocyte chemoattractant protein-1 is sufficient for the chemotaxis of monocytes and lymphocytes in transgenic mice but requires an additional stimulus for inflammatory activation.

Journal Article J Immunol · January 1, 1997 Monocyte chemoattractant protein-1 (MCP-1), a chemotactic cytokine, acts in vitro as a chemotactic and activating factor for multiple types of leukocytes. To determine the chemotactic and activating effects of MCP-1 in vivo, we constructed transgenic mice ... Link to item Cite

Endothelin activates voltage-dependent Ca2+ current by a G protein-dependent mechanism in rabbit cardiac myocytes.

Journal Article J Physiol · March 1992 1. Endothelin is a vasoactive peptide released from vascular endothelial cells which has potent cardiac inotropic effects. We examined the effect of endothelin on the verapamil-sensitive Ca2+ current (ICa) in enzymatically dispersed rabbit ventricular myoc ... Full text Link to item Cite

A truncated form of fibroblast growth factor receptor 1 inhibits signal transduction by multiple types of fibroblast growth factor receptor.

Journal Article J Biol Chem · January 25, 1992 A truncated form of the type 1 fibroblast growth factor receptor (FGFR1) lacking most of its cytoplasmic domain was tested for its ability to inhibit signal transduction by each of three different wild-type FGFRs (FGFR1, 2, and 3). When the truncated FGFR1 ... Link to item Cite

Mechanisms of accumulation of arachidonic acid in cultured myocardial cells during ATP depletion.

Journal Article Am J Physiol · December 1985 Previous studies have suggested that the accumulation of free arachidonic acid may be of major importance in the pathophysiology of myocardial ischemia. The purpose of the present study was to determine if the release of arachidonic acid from myocardial ce ... Full text Link to item Cite

Mechanisms of accumulation of arachidonic acid in cultured myocardial cells during ATP depletion

Journal Article American Journal of Physiology - Heart and Circulatory Physiology · December 1, 1985 Previous studies have suggested that the accumulation of free arachidonic acid may be of major importance in the pathophysiology of myocardial ischemia. The purpose of the present study was to determine if the release of arachidonic acid from myocardial ce ... Cite

Release of arachidonate from membrane phospholipids in cultured neonatal rat myocardial cells during adenosine triphosphate depletion. Correlation with the progression of cell injury.

Journal Article J Clin Invest · June 1985 The present study utilized a cultured myocardial cell model to evaluate the relationship between the release of arachidonate from membrane phospholipids, and the progression of cell injury during ATP depletion. High-energy phosphate depletion was induced b ... Full text Link to item Cite