Thomas A. Wynn, Ph.D.
Chief, Immunopathogenesis Section
Senior Investigator
Immunopathogenesis Section
Description of Research Program
 |
| Arginase-1-expressing macrophages function as suppressor cells during helminth infection. Mice deficient in Arginase-1 in macrophages (Arg1-/flox; LysMcre) fail to downregulate the egg-induced inflammatory response when chronically infected with Schistosoma mansoni. The Arg1-/flox; LysMcre also develop severe liver fibrosis, as shown here by second harmonic emission confocal microscopy. The image shows extensive collagen deposition around schistosome eggs lodged in the liver (see Pesce et al., doi:10.1371/journal.ppat.1000371). Credit: NIAID |
Research in the Immunopathogenesis Section is focused on understanding the molecular and immunological mechanisms of fibrosis in schistosomiasis and other chronic fibrotic diseases.
Tissue fibrosis or scarring is a leading cause of morbidity and mortality worldwide. Current health statistics suggest that nearly 45 percent of all natural deaths in the western world are attributable to some type of chronic fibroproliferative disease. Fibrosis affects nearly all tissues and organ systems. Diseases in which fibrosis is a major cause of morbidity and mortality include the interstitial lung diseases, liver cirrhosis, kidney disease, heart disease, and systemic sclerosis, among others. Fibrotic tissue remodeling can also influence cancer metastasis and accelerate chronic graft rejection in transplant recipients.
Specific aims of the Immunopathogenesis Section include the following:
- Characterize the IL-13-dependent pathway of fibrosis and elucidate the function of novel downstream target genes that are regulated by Th2-associated cytokines, including Arginase-1.
- Elucidate the role of alternatively activated macrophages in tissue remodeling, inflammation, and fibrosis.
- Identify common and unique mechanisms of fibrosis in various organ systems and/or diseases, including severe asthma, idiopathic pulmonary fibrosis, and systemic sclerosis.
- Compare mechanisms of granulomatous inflammation and fibrosis in tuberculosis and schistosomiasis.
- Translate findings from mice to humans by establishing relevant preclinical models of fibrosis, so that novel therapies for schistosomiasis and other chronic fibroproliferative disorders might be evaluated quantitatively, in vivo, over time.
The group uses transgenic and knockout mice to elucidate the mechanisms of fibrosis and Th2-dependent immunity in vivo.
We are always looking for enthusiastic new investigators to join our group. Contact Dr. Wynn to learn more about the research projects currently available.
Research Group Members
Left to right: Luke Barron, Satish Madala, Tom Wynn, Margaret Mentink-Kane, Thiru Ramalingam, Rob Thompson, and Mark Wilson
Selected Recent Publications
(View list in PubMed.)
Pesce JT, Ramalingam TR, Mentink-Kane MM, Wilson MS, El Kasmi KC, Smith AM, Thompson RW, Cheever AW, Murray PJ, Wynn TA. Arginase-1-expressing macrophages suppress Th2 cytokine-driven inflammation and fibrosis. PLoS Pathog. 2009 Apr;5(4):e1000371. Epub 2009 Apr 10.
El Kasmi KC, Qualls JE, Pesce JT, Smith AM, Thompson RW, Henao-Tamayo M, Basaraba RJ, König T, Schleicher U, Koo MS, Kaplan G, Fitzgerald KA, Tuomanen EI, Orme IM, Kanneganti TD, Bogdan C, Wynn TA, Murray PJ. Toll-like receptor-induced arginase 1 in macrophages thwarts effective immunity against intracellular pathogens. Nat Immunol. 2008 Dec;9(12):1399-406. Epub 2008 Nov 2.
Ramalingam TR, Pesce JT, Sheikh F, Cheever AW, Mentink-Kane MM, Wilson MS, Stevens S, Valenzuela DM, Murphy AJ, Yancopoulos GD, Urban JF Jr, Donnelly RP, Wynn TA. Unique functions of the type II interleukin 4 receptor identified in mice lacking the interleukin 13 receptor alpha1 chain. Nat Immunol. 2008 Jan;9(1):25-33.
Wilson MS, Elnekave E, Mentink-Kane MM, Hodges MG, Pesce JT, Ramalingam TR, Thompson RW, Kamanaka M, Flavell RA, Keane-Myers A, Cheever AW, Wynn TA.IL-13Ralpha2 and IL-10 coordinately suppress airway inflammation, airway-hyperreactivity, and fibrosis in mice. J Clin Invest. 2007 Oct;117(10):2941-51.
Wynn TA. Common and unique mechanisms regulate fibrosis in various fibroproliferative diseases. J Clin Invest. 2007 Mar;117(3):524-9.
Pesce J, Kaviratne M, Ramalingam TR, Thompson RW, Urban JF, Cheever AW, Young DA, Collins M, Grusby MJ, Wynn TA . The IL-21 receptor augments Th2 effector function and alternative macrophage activation. J Clin Invest. 2006 Jul;116(7):2044-55. Epub 2006 Jun 15.
back to top