Scholars

Wynn, Thomas Anthony, Ph.D.

Senior Investigator

Positions:

Senior Investigator, Immunopathogenesis Section

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overview

Dr. Wynn is a senior investigator and chief of the Immunopathogenesis Section of the Laboratory of Parasitic Diseases. He also serves as the scientific director of the NIH-Oxford-Cambridge Scholars program, a doctoral training program for outstanding science students committed to biomedical research, which annually supports more than 64 doctoral candidates at NIH, Oxford University, and Cambridge University. Dr. Wynn obtained his Ph.D. from the University of Wisconsin-Madison Medical School in the department of microbiology and immunology. His laboratory group uses in vivo model systems to study the immunological mechanisms of inflammation and fibrosis. He has published over 200 papers, reviews, and book chapters in many prestigious journals, including Nature, Nature Immunology, Journal of Experimental Medicine, Gastroenterology, Nature Reviews Immunology, Nature Medicine, and Annual Review of Immunology. He has made important contributions to our understanding of the role of IL-13, IL-17A, and macrophages in the pathogenesis of fibrosis in multiple organ systems and has developed clinically relevant models to test novel anti-fibrotic drugs. His group collaborates extensively with the pharmaceutical industry to accelerate the translation of basic science discoveries into novel treatments for patients. Dr. Wynn was elected to fellowship in the American Academy of Microbiology in 2013 and has received several prestigious awards, including the Bailey K. Ashford Medal from the American Society of Tropical Medicine and Hygiene, the Oswaldo Cruz Medal from the Oswaldo Cruz Foundation, and two Merit Awards from NIH. Dr. Wynn has organized several national and international scientific meetings, including three Keystone Symposia and the first Aegean conference on Tissue Repair, Regeneration, and Fibrosis.

selected publications

Academic Articles218

(2020). Opinion on Immune Tolerance Therapeutic Development. TOXICOLOGIC PATHOLOGY. 48(6), 712-717.
(2020). Metformin and 2-Deoxyglucose Collaboratively Suppress Human CD4(+) T Cell Effector Functions and Activation-Induced Metabolic Reprogramming. JOURNAL OF IMMUNOLOGY. 205(4), 957-967.
(2019). Anti-IL-13R alpha 2 therapy promotes recovery in a murine model of inflammatory bowel disease. Mucosal Immunology. 12(5), 1174-1186.
(2019). Fibroblast-specific integrin-alpha V differentially regulates type 17 and type 2 driven inflammation and fibrosis. JOURNAL OF PATHOLOGY. 248(1), 16-29.
(2019). Heat shock protein 70 is a positive regulator of airway inflammation and goblet cell hyperplasia in a mouse model of allergic airway inflammation. JOURNAL OF BIOLOGICAL CHEMISTRY. 294(41), 15082-15094.
(2019). IMMUNOLOGY Two types of fibroblast drive arthritis. NATURE. 570(7760), 169-170.
(2018). Type 2 immunity in tissue repair and fibrosis. NATURE REVIEWS IMMUNOLOGY.
(2018). Ym1 induces RELM alpha and rescues IL-4R alpha deficiency in lung repair during nematode infection. PLoS Pathogens. 14(11),
(2017). Accurately measuring and modeling Th2 and Th17 endotypes in severe asthma. Annals of Translational Medicine. 5(4),
(2017). Cutting Edge: Eosinophils Undergo Caspase-1-Mediated Pyroptosis in Response to Necrotic Liver Cells. JOURNAL OF IMMUNOLOGY. 199(3), 847-853.
(2017). Inflammation and metabolism in tissue repair and regeneration. SCIENCE. 356(6342), 1026-1030.
(2017). Mechanisms of Organ Injury and Repair by Macrophages. Annual Review of Physiology. 79, 593-617.
(2017). Radiation-Induced Fibrosis: Mechanisms and Opportunities to Mitigate. Report of an NCI Workshop, September 19, 2016. RADIATION RESEARCH. 188(1), 1-20.
(2017). Reconstruction of the mouse extrahepatic biliary tree using primary human extrahepatic cholangiocyte organoids. NATURE MEDICINE. 23(8), 954-+.
(2017). Repetitive intradermal bleomycin injections evoke T-helper cell 2 cytokine-driven pulmonary fibrosis. AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY. 313(5), L796-L806.
(2017). T Cells Encountering Myeloid Cells Programmed for Amino Acid-dependent Immunosuppression Use Rictor/mTORC2 Protein for Proliferative Checkpoint Decisions. JOURNAL OF BIOLOGICAL CHEMISTRY. 292(1), 15-30.
(2017). Type 2 immunity is protective in metabolic disease but exacerbates NAFLD collaboratively with TGF-beta. Science Translational Medicine. 9(396),
(2016). Acidic chitinase primes the protective immune response to gastrointestinal nematodes. NATURE IMMUNOLOGY. 17(5), 538-+.
(2016). Breaking the Mold: Partnering with the National Institutes of Health Intramural Research Program to Accelerate PhD Training. TRENDS IN IMMUNOLOGY. 37(12), 813-815.
(2016). Combinatorial targeting of TSLP, IL-25, and IL-33 in type 2 cytokine-driven inflammation and fibrosis. Science Translational Medicine. 8(337),
(2016). Enhanced protection from fibrosis and inflammation in the combined absence of IL-13 and IFN-gamma. JOURNAL OF PATHOLOGY. 239(3), 344-354.
(2016). IL-13 is a therapeutic target in radiation lung injury. Scientific Reports. 6,
(2016). IL4I1 augments CNS remyelination and axonal protection by modulating T cell driven inflammation. BRAIN. 139, 3121-3136.
(2016). Interleukin-13 Activates Distinct Cellular Pathways Leading to Ductular Reaction, Steatosis, and Fibrosis. IMMUNITY. 45(1), 145-158.
(2016). Interleukin-13 Receptor alpha 1-Dependent Responses in the Intestine Are Critical to Parasite Clearance. INFECTION AND IMMUNITY. 84(4), 1032-1044.
(2016). Macrophages are critical to the maintenance of IL-13-dependent lung inflammation and fibrosis. Mucosal Immunology. 9(1), 38-55.
(2016). Macrophages in Tissue Repair, Regeneration, and Fibrosis. IMMUNITY. 44(3), 450-462.
(2016). Type 2 Interleukin-4 Receptor Signaling in Neutrophils Antagonizes Their Expansion and Migration during Infection and Inflammation. IMMUNITY. 45(1), 172-184.
(2015). Biomarker and Therapeutic Potential of CSF1 in Acute Liver Failure. GASTROENTEROLOGY. 149(7), 1675-1678.
(2015). IL-25 or IL-17E Protects against High-Fat Diet-Induced Hepatic Steatosis in Mice Dependent upon IL-13 Activation of STAT6. JOURNAL OF IMMUNOLOGY. 195(10), 4771-4780.
(2015). T(H)2 and T(H)17 inflammatory pathways are reciprocally regulated in asthma. Science Translational Medicine. 7(301),
(2015). The polymeric mucin Muc5ac is required for allergic airway hyperreactivity. Nature Communications. 6,
(2015). Type 2 cytokines: mechanisms and therapeutic strategies. NATURE REVIEWS IMMUNOLOGY. 57(7291), 1035-1250.
(2014). Adaptation of Innate Lymphoid Cells to a Micronutrient Deficiency Promotes Type 2 Barrier Immunity. SCIENCE. 343(6169), 432-437.
(2014). Conventional NK Cells Can Produce IL-22 and Promote Host Defense in Klebsiella pneumoniae Pneumonia. JOURNAL OF IMMUNOLOGY. 192(4), 1778-1786.
(2014). Future Directions in Idiopathic Pulmonary Fibrosis Research. AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE. 189(2), 214-222.
(2014). Genetic deletion of IL-25 (IL-17E) confers resistance to dextran sulfate sodium-induced colitis in mice. Cell and Bioscience. 4,
(2014). IL-1 alpha released from damaged epithelial cells is sufficient and essential to trigger inflammatory responses in human lung fibroblasts. Mucosal Immunology. 7(3), 684-693.
(2014). IL-21 receptor signalling partially mediates Th2-mediated allergic airway responses. CLINICAL AND EXPERIMENTAL ALLERGY. 44(7), 976-985.
(2014). Incomplete Deletion of IL-4R alpha by LysM(Cre) Reveals Distinct Subsets of M2 Macrophages Controlling Inflammation and Fibrosis in Chronic Schistosomiasis. PLoS Pathogens. 10(9),
(2014). Macrophage Activation and Polarization: Nomenclature and Experimental Guidelines. IMMUNITY. 41(1), 14-20.
(2014). Maturation of Induced Pluripotent Stem Cell Derived Hepatocytes by 3D-Culture. PLoS One. 9(1),
(2014). TNF-alpha/IL-17 synergy inhibits IL-13 bioactivity via IL-13R alpha 2 induction. JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY. 134(4), 975-978.
(2014). The TNF-family cytokine TL1A promotes allergic immunopathology through group 2 innate lymphoid cells. Mucosal Immunology. 7(4), 958-968.
(2013). A Trypanosoma brucei Kinesin Heavy Chain Promotes Parasite Growth by Triggering Host Arginase Activity. 9(10),
(2013). An efferocytosis-induced, IL-4-dependent macrophage-iNKT cell circuit suppresses sterile inflammation and is defective in murine CGD. BLOOD. 121(17), 3473-3483.
(2013). Cytokine mediated tissue fibrosis. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE. 1832(7), 1049-1060.
(2013). Host Responses in Tissue Repair and Fibrosis. Annual Review of Pathology-Mechanisms of Disease. 8, 241-276.
(2013). IL-33-induced alterations in murine intestinal function and cytokine responses are MyD88, STAT6, and IL-13 dependent. AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY. 304(4), G381-G389.
(2013). Macrophage biology in development, homeostasis and disease. NATURE. 496(7446), 445-455.
(2013). Macrophages as IL-25/IL-33-Responsive Cells Play an Important Role in the Induction of Type 2 Immunity. PLoS One. 8(3),
(2013). Myeloid-cell differentiation redefined in cancer. NATURE IMMUNOLOGY. 14(3), 197-199.
(2013). Role of Arginase 1 from Myeloid Cells in Th2-Dominated Lung Inflammation. PLoS One. 8(4),
(2013). Transforming Growth Factor-beta Signaling Promotes Pulmonary Hypertension Caused by Schistosoma Mansoni. CIRCULATION. 128(12), 1354-1364.
(2013). Type 2 immunity and wound healing: evolutionary refinement of adaptive immunity by helminths. NATURE REVIEWS IMMUNOLOGY. 13(8), 607-614.
(2013). miR-182 and miR-10a Are Key Regulators of Treg Specialisation and Stability during Schistosome and Leishmania-associated Inflammation. PLoS Pathogens. 9(6),
(2012). Alternatively activated dendritic cells regulate CD4(+) T-cell polarization in vitro and in vivo. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. 109(25), 9977-9982.
(2012). An essential role for T(H)2-type responses in limiting acute tissue damage during experimental helminth infection. NATURE MEDICINE. 18(2), 260-266.
(2012). Chitinase Dependent Control of Protozoan Cyst Burden in the Brain. PLoS Pathogens. 8(11),
(2012). Investigation of the binding pocket of human hematopoietic prostaglandin (PG) D2 synthase (hH-PGDS): A tale of two waters. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS. 22(11), 3795-3799.
(2012). Mechanisms of fibrosis: therapeutic translation for fibrotic disease. NATURE MEDICINE. 18(7), 1028-1040.
(2012). Molecular mimicry between cockroach and helminth glutathione S-transferases promotes cross-reactivity and cross-sensitization. JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY. 130(1), 248-+.
(2012). RGS16 Attenuates Pulmonary Th2/Th17 Inflammatory Responses. JOURNAL OF IMMUNOLOGY. 188(12), 6347-6356.
(2011). Accelerated and Progressive and Lethal Liver Fibrosis in Mice That Lack Interleukin (IL)-10, IL-12p40, and IL-13R alpha 2. GASTROENTEROLOGY. 141(6), 2200-2209.
(2011). Colitis and Intestinal Inflammation in IL10(-/-) Mice Results From IL-13R alpha 2-Mediated Attenuation of IL-13 Activity. GASTROENTEROLOGY. 140(1), 254-+.
(2011). Evolution of Th2 Immunity: A Rapid Repair Response to Tissue Destructive Pathogens. PLoS Pathogens. 7(5),
(2011). Fibrosis is regulated by Th2 and Th17 responses and by dynamic interactions between fibroblasts and macrophages. AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY. 300(5), G723-G728.
(2011). IL-10 Blocks the Development of Resistance to Re-Infection with Schistosoma mansoni. PLoS Pathogens. 7(8),
(2011). Integrating mechanisms of pulmonary fibrosis. JOURNAL OF EXPERIMENTAL MEDICINE. 208(7), 1339-1350.
(2011). Macrophage activation governs schistosomiasis-induced inflammation and fibrosis. EUROPEAN JOURNAL OF IMMUNOLOGY. 41(9), 2509-2514.
(2011). Mapping mouse IL-13 binding regions using structure modeling, molecular docking, and high-density peptide microarray analysis. PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS. 79(1), 282-293.
(2011). Muc5ac: a critical component mediating the rejection of enteric nematodes. JOURNAL OF EXPERIMENTAL MEDICINE. 208(5), 893-900.
(2011). Obstacles and opportunities for understanding macrophage polarization. JOURNAL OF LEUKOCYTE BIOLOGY. 89(4), 557-563.
(2011). Phenotypic and functional plasticity of cells of innate immunity: macrophages, mast cells and neutrophils. NATURE IMMUNOLOGY. 12(11), 1035-1044.
(2011). Protective and pathogenic functions of macrophage subsets. NATURE REVIEWS IMMUNOLOGY. 11(11), 723-737.
(2011). Regulation of Macrophage Arginase Expression and Tumor Growth by the Ron Receptor Tyrosine Kinase. JOURNAL OF IMMUNOLOGY. 187(5), 2181-2192.
(2011). Shedding LIGHT on severe asthma. NATURE MEDICINE. 17(5), 547-548.
(2011). Strain-Dependent Genomic Factors Affect Allergen-Induced Airway Hyperresponsiveness in Mice. AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY. 45(4), 817-824.
(2011). The TNF-family cytokine TL1A drives IL-13-dependent small intestinal inflammation. Mucosal Immunology. 4(2), 172-185.
(2010). Bleomycin and IL-1 beta-mediated pulmonary fibrosis is IL-17A dependent. JOURNAL OF EXPERIMENTAL MEDICINE. 207(3), 535-552.
(2010). Blood Fluke Exploitation of Non-Cognate CD4(+) T Cell Help to Facilitate Parasite Development. PLoS Pathogens. 6(4),
(2010). Critical Role of IL-25 in Nematode Infection-Induced Alterations in Intestinal Function. JOURNAL OF IMMUNOLOGY. 185(11), 6921-6929.
(2010). Fibrosis under arrest. NATURE MEDICINE. 16(5), 523-525.
(2010). Macrophages: Master Regulators of Inflammation and Fibrosis. SEMINARS IN LIVER DISEASE. 30(3), 245-257.
(2010). Matrix Metalloproteinase 12-Deficiency Augments Extracellular Matrix Degrading Metalloproteinases and Attenuates IL-13-Dependent Fibrosis. JOURNAL OF IMMUNOLOGY. 184(7), 3955-3963.
(2010). Redundant and Pathogenic Roles for IL-22 in Mycobacterial, Protozoan, and Helminth Infections. JOURNAL OF IMMUNOLOGY. 184(8), 4378-4390.
(2010). Schistosomiasis-Induced Experimental Pulmonary Hypertension Role of Interleukin-13 Signaling. AMERICAN JOURNAL OF PATHOLOGY. 177(3), 1549-1561.
(2009). Arginase-1-Expressing Macrophages Suppress Th2 Cytokine-Driven Inflammation and Fibrosis. PLoS Pathogens. 5(4),
(2009). Basophils trump dendritic cells as APCs for T(H)2 responses. NATURE IMMUNOLOGY. 10(7), 679-681.
(2009). IL-13 Receptor alpha 2 Regulates the Immune and Functional Response to Nippostrongylus brasiliensis Infection. JOURNAL OF IMMUNOLOGY. 183(3), 1934-1939.
(2009). Pulmonary fibrosis: pathogenesis, etiology and regulation. Mucosal Immunology. 2(2), 103-121.
(2009). Regulation of Helminth-Induced Th2 Responses by Thymic Stromal Lymphopoietin. JOURNAL OF IMMUNOLOGY. 182(10), 6452-6459.
(2009). Regulation of pathogenesis and immunity in helminth infections. JOURNAL OF EXPERIMENTAL MEDICINE. 206(10), 2059-2066.
(2009). Retnla (Relm alpha/Fizz1) Suppresses Helminth-Induced Th2-Type Immunity. PLoS Pathogens. 5(4),
(2009). Schistosoma mansoni arginase shares functional similarities with human orthologs but depends upon disulphide bridges for enzymatic activity. INTERNATIONAL JOURNAL FOR PARASITOLOGY. 39(3), 267-279.
(2009). The Adaptor Protein CIKS/Act1 Is Essential for IL-25-Mediated Allergic Airway Inflammation. JOURNAL OF IMMUNOLOGY. 182(3), 1617-1630.
(2008). A novel and sensitive ELISA reveals that the soluble form of IL-13R-alpha 2 is not expressed in plasma of healthy or asthmatic subjects. CLINICAL AND EXPERIMENTAL ALLERGY. 38(4), 594-601.
(2008). Cationic amino acid transporter-2 regulates immunity by modulating arginase activity. PLoS Pathogens. 4(3),
(2008). Cellular and molecular mechanisms of fibrosis. JOURNAL OF PATHOLOGY. 214(2), 199-210.
(2008). Chronic graft-versus-host disease: How can we release Prometheus?. BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION. 14(1), 142-+.

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Academic Articles218