Although IL-13 clearly plays an important role in the schistosomiasis model, it remains unclear to what extent targeting this pathway might be useful in the treatment of other fibroproliferative diseases. Therefore, we have begun to investigate the role of Th2-type cytokines in other models of fibrosis to determine whether there are common as well as distinct mechanisms of fibrosis in various organ systems and/or diseases. The models that were set up in the lab over the past few years include a mouse model of chronic asthma, which is being used to investigate the mechanisms pulmonary remodeling in response to chronic allergen challenge, the bleomycin models of lung and skin fibrosis, and several models if intestinal inflammation. Projects completed during the past year: Two reviews on fibrosis were completed in the previous year. These reviews appeared in Nature Medicine and Nature Immunology. Active projects: 1. Transgenic and knockout mice are being used to explore the mechanisms of fibrosis in model of chronic graft rejection. 2. Studies are underway to explore the mechanisms of muscle and lung fibrosis following radiation therapy. 3. Studies are underway to examine the mechanisms of intestinal fibrosis in models of chronic inflammatory bowel disease.
| Gieseck 3rd, Richard L; Wilson, Mark S; Wynn, Thomas A (2018) Type 2 immunity in tissue repair and fibrosis. Nat Rev Immunol 18:62-76 |
| Vannella, Kevin M; Wynn, Thomas A (2017) Mechanisms of Organ Injury and Repair by Macrophages. Annu Rev Physiol 79:593-617 |
| Singh, Brijendra; Kasam, Rajesh K; Sontake, Vishwaraj et al. (2017) Repetitive intradermal bleomycin injections evoke T-helper cell 2 cytokine-driven pulmonary fibrosis. Am J Physiol Lung Cell Mol Physiol 313:L796-L806 |
| Eming, Sabine A; Wynn, Thomas A; Martin, Paul (2017) Inflammation and metabolism in tissue repair and regeneration. Science 356:1026-1030 |
| Hart, Kevin M; Choy, David F; Bradding, Peter et al. (2017) Accurately measuring and modeling Th2 and Th17 endotypes in severe asthma. Ann Transl Med 5:91 |
| Citrin, Deborah E; Prasanna, Pataje G S; Walker, Amanda J et al. (2017) Radiation-Induced Fibrosis: Mechanisms and Opportunities to Mitigate. Report of an NCI Workshop, September 19, 2016. Radiat Res 188:1-20 |
| Hart, Kevin M; Fabre, Thomas; Sciurba, Joshua C et al. (2017) Type 2 immunity is protective in metabolic disease but exacerbates NAFLD collaboratively with TGF-?. Sci Transl Med 9: |
| Wynn, Thomas A; Vannella, Kevin M (2016) Macrophages in Tissue Repair, Regeneration, and Fibrosis. Immunity 44:450-462 |
| Chung, Su I; Horton, Jason A; Ramalingam, Thirumalai R et al. (2016) IL-13 is a therapeutic target in radiation lung injury. Sci Rep 6:39714 |
| Vannella, Kevin M; Ramalingam, Thirumalai R; Hart, Kevin M et al. (2016) Acidic chitinase primes the protective immune response to gastrointestinal nematodes. Nat Immunol 17:538-44 |
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