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Thomas A. Wynn, Ph.D.

Photo of Thomas A. Wynn, Ph.D. 

Chief, Immunopathogenesis Section
Laboratory of Parasitic Diseases
Scientific Director, NIH Oxford-Cambridge Scholars Program

Major Areas of Research

  • Type-2 immunity and wound repair
  • Asthma and idiopathic pulmonary fibrosis
  • Liver fibrosis
  • Intestinal fibrosis in inflammatory bowel disease
  • Stem cells and tissue regeneration

Program Description

Illustration:Mechanisms Driving Major Macrophage Activation Phenotypes in Tissue Repair, Regeneration, and Fibrosis
Mechanisms Driving Major Macrophage Activation Phenotypes in Tissue Repair, Regeneration, and Fibrosis
In many tissues, the tissue-resident macrophage population is derived from the yolk sac and fetal liver during development but is complimented by inflammatory monocytes recruited from the bone marrow after injury. The recruited and resident macrophages undergo marked phenotypic and functional changes in response to DAMPs, PAMPs, growth factors, cytokines, and other mediators released in the local tissue microenvironment. The dominant phenotypic variants depicted here regulate inflammation, tissue repair, regeneration, and resolution. Macrophages produce a variety of factors that stimulate the proliferation, differentiation, and activation of fibroblasts, epithelial cells, endothelial cells, and stem and progenitor cells that facilitate tissue repair. During the later stages of the repair process, they assume a regulatory pro-resolving phenotype that ensures that the tissue-damaging inflammatory response is suppressed and normal tissue architecture is restored. If the process is not controlled effectively, persistent inflammation and/or maladaptive repair processes can lead to tissue-destructive fibrosis. In some cases, the recruited monocytes seed the tissues and adopt a resident macrophage phenotype; however, the mechanisms that restore tissue homeostasis are still under debate. From Wynn and Vannella, Immunity. 2016 Mar 15;44(3):450-62. doi: 10.1016/j.immuni.2016.02.015.

The researchers in the Immunopathogenesis Section (IPS) in LPD/NIAID investigate the immunological and molecular mechanisms of fibrosis, a major cause of morbidity and mortality in many chronic diseases, including asthma, liver cirrhosis, cardiovascular disease, idiopathic pulmonary fibrosis, Crohn’s disease, and ulcerative colitis. The ultimate goal of our research program is to identify novel therapies for fibrotic diseases, for which few viable therapeutic strategies currently exist. The IPS research program relies heavily on transgenic and knockout mouse models to dissect the mechanisms of fibrosis and focuses on three major organs systems, including the liver, lung, and gastrointestinal tract. We also utilize a variety of biopsy tissues obtained from patients suffering from various forms of progressive fibrotic disease.

Fibrotic tissue remodeling is the final common pathological outcome of many chronic inflammatory and infectious diseases. Although the synthesis of extracellular matrix components like collagen is an indispensable and, typically, reversible part of all wound-healing responses, normal tissue repair can evolve into a progressively irreversible fibrotic response if the tissue injury is severe or repetitive or if the wound-healing response itself becomes dysregulated. Indeed, tissue repair and regeneration are critical biological processes that are fundamental to the survival of all living organisms. When tissues are injured during infection or after toxic or mechanical injury, an inflammatory response is induced in response to damage-associated molecular patterns and pathogen-associated molecular patterns released by dead and dying cells and invading organisms, respectively. These molecular triggers induce a complex inflammatory response that is characterized by the recruitment, proliferation, and activation of a variety of hematopoietic and non-hematopoietic cells, including neutrophils, macrophages, innate lymphoid cells, natural killer cells, B cells, T cells, fibroblasts, epithelial cells, endothelial cells, stem cells, and specialized tissue progenitor cells, which together make up the cellular response that orchestrates tissue repair. When the wound-healing response is well organized and controlled, the inflammatory response resolves quickly, and normal tissue architecture is restored. However, if the wound-healing response is chronic or becomes dysregulated, it can lead to the development of pathological fibrosis or scarring, impairing normal tissue function and ultimately leading to organ failure and death. Therefore, wound-healing responses must be tightly regulated. Although fibrogenesis is increasingly recognized as a major cause of morbidity and mortality, there are few—if any—treatment strategies that specifically target the mechanisms of fibrosis, despite the fact that nearly 45 percent of all deaths in the developed world are attributable to fibroproliferative disorders.

The IPS investigates the mechanisms of tissue regeneration and fibrosis and is particularly interested in understanding the role of stem cells and tissue progenitor cells in wound-repair responses more generally. As we were the first group to demonstrate a central and indispensable role for IL-13 in the development of fibrosis, our research program continues to focus on IL-13 biology, with particular emphasis on the role of the IL-13 signaling and decoy receptors. Identifying the key cellular targets of IL-13 has also been emphasized in our research, as we hypothesize that any intervention that disrupts critical steps in the IL-13 response might emerge as a viable therapeutic strategy for fibrosis.

Specific aims of the IPS include the following:

  • Identify core mechanisms of fibrosis in various organ systems and/or diseases, including persistent asthma, idiopathic pulmonary fibrosis, liver fibrosis, and inflammatory bowel disease
  • Characterize the IL-13 pathway of fibrosis and elucidate the function of novel downstream target genes that are regulated by Th2-associated cytokines
  • Understand the link between inflammatory mediators like IL-1, TNF-alpha, and IL-17 and the core pro-fibrotic cytokines TGF-beta and IL-13 in various types of fibrosis
  • Elucidate the role of monocyte and macrophage subsets in wound healing, chronic inflammation, and fibrosis progression and resolution
  • Investigate the therapeutic potential of macrophages and stem/tissue progenitor cells in tissue regeneration and fibrosis
  • Translate findings from mice to humans by establishing relevant preclinical models of fibrosis, so that novel therapies for liver fibrosis and other chronic fibroproliferative disorders might be evaluated

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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.

Research Group

Photo of LPD group members
L to R back row: Kevin Vannella, Sandy White, David Cantu, Rob Thompson, and Josh Sciurba
Middle row: Trisha Pasricha, Luke Barron, Trey Gieseck, and Kevin Hart
Front row: Tom Wynn, Casey Rimland, Nikhil Jiwrajka, and Thiru Ramalingam

Publications and Patents


Vannella KM, Ramalingam TR, Hart KM, deQueiroz Prado R, Sciurba J, Barron L, Borthwick LA, Smith AD, Mentink-Kane M, White S, Thomson RW, Cheever AW, Bock K, Moore I, Fitz LJ, Urban JF Jr., Wynn TA. Acidic chitinase primes the protective immune response to gastrointestinal nematodes. Nat Immunol. 2016 Apr 4. Epub ahead of print.

Wynn TA, Vannella KM. Macrophages in tissue repair, regeneration, and fibrosis. Immunity. 2016 Mar 15;44(3):450-62.

Choy DF, Hart KM, Borthwick LA, Shikotra A, Nagarkar DR, Siddiqui S, Jia G, Ohri CM, Doran E, Vannella KM, Butler CA, Hargadon B, Sciurba JC, Gieseck RL, Thompson RW, White S, Abbas AR, Jackman J, Wu LC, Egen JG, Heaney LG, Ramalingam TR, Arron JR, Wynn TA, Bradding P. TH2 and TH17 inflammatory pathways are reciprocally regulated in asthma. Sci Transl Med. 2015 Aug 19;7(301):301ra129.

Wynn TA. Type 2 cytokines: mechanisms and therapeutic strategies.Nat Rev Immunol. 2015 May;15(5):271-82.

Wynn TA, Chawla A, Pollard JW. Macrophage biology in development, homeostasis and disease.Nature. 2013 Apr 25;496(7446):445-55.

Visit PubMed for a complete publication list.


Young DA, Wynn TA, Collins M, Grusby MJ., inventors; Wyeth LCC, The United States of America as represented by the Department of Health and Human Services, assignee. Methods for treating and preventing fibrosis. United States patent US 7,910,105. 2011 Mar 22.

Wynn TA, Chiaramonte MG, Collins M, Donaldson D, Fitz L, Neben T, Whitters MJ, Wood C, inventors; Wyeth, The United States of America as represented by the Department of Health and Human Services, assignee. Treatment of fibrosis by antagonism of IL-13 and IL-13 receptor chains. United States patent US 7,282,206. 2007 Oct 16.

Wynn TA, Chiaramonte MG, Collins M, Donaldson D, Fitz L, Neben T, Whitters MJ, Wood C, inventors; Wyeth, The United States of America as represented by the Department of Health and Human Services, assignee. Treatment of fibrosis by antagonism of IL-13 and IL-13 receptor chains. United States patent US 6,664,227. 2003 Dec 16.

Featured Research

photo of airway inflammation in lung samples from a mouse model of asthma 

Enzyme Initiates Protective Immune Responses Against Gut Parasites

Researchers describe the role of the enzyme acidic mammalian chitinase, or AMCase, in initiating protective immune responses against certain parasitic gut infections. The findings in mice suggest that AMCase, which had previously been implicated in allergic lung disease, is critical for defense against gastrointestinal helminth infections.

photo of airway inflammation in lung samples from a mouse model of asthma 

Researchers Refine How Immune Pathways Contribute to Asthma

Researchers show that targeting two immune cells—Th2 and Th17—and their downstream, inflammatory effects is better than targeting just one pathway in the context of asthma. These results clarify how immune cells and their products contribute to asthma, advancing therapeutic research for asthma and other inflammatory diseases.

photo of an inhaler 

Reducing Airway Mucus Alleviates Asthma in Mouse Study

Researchers show that overproduction of a specific mucus, MUC5AC, is responsible for asthma symptoms in mice. If the results hold true in people, targeting airway mucus production may offer a new strategy for treating asthma.

illustration of a lung 

A Breath of Fresh Air: Targeting the Immune System to Treat Pulmonary Fibrosis

NIAID researchers are examining the role of the immune system in the development of idiopathic pulmonary fibrosis (IPF), a life-threatening lung disorder that has no cure and few treatment options.

Last Updated April 21, 2016