Distinct roles for IL-13 and IL-17 in chronic inflammation and fibrosis (134.8)
| Autor: | Thomas Wynn, Thirumalai Ramalingam, Satish Madala, Robert Thompson, Margaret Mentink, Luke Barron, Allen Cheever, Mark Wilson |
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| Rok vydání: | 2010 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 184:134.8-134.8 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | TH2 cytokines regulate inflammation, mucus production, tissue remodeling, and fibrosis. Consequently, they have become important therapeutic targets for a number of debilitating illnesses, including asthma, idiopathic pulmonary fibrosis, ulcerative colitis, liver fibrosis, and other diseases in which TH2 cytokines are over-produced. In schistosomiasis, numerous studies have shown that TH2 cytokines play a critical role in the pathogenesis of the disease. Thus, understanding how the TH2 cytokine response is regulated during infection as well as the mechanism of action of each TH2 cytokine (IL-4, IL-5, IL-9, IL-10, IL-13, IL-21, IL-25) has been a major goal of our group over the past several years. Interestingly, in contrast to schistosomiasis-induced lung and liver fibrosis, bleomycin induced pulmonary fibrosis is associated with the development of an IL-17A-producing CD4+ and γδ+ T cell response. Studies conducted with C57BL/6 il17a-/- mice confirmed an essential role for IL-17A in bleomycin-induced fibrosis. Bleomycin-induced IL-17A production was also TGFβ dependent and recombinant IL- 17A-mediated fibrosis required TGFβ, suggesting cooperative roles for IL-17A and TGFβ in the development of fibrosis. We also found that fibrosis induced by IL-1β, which mimics bleomycin-induced fibrosis, is highly dependent on IL-17A. Together, these results suggest distinct non-overlapping immunological roles for IL-13 and IL-17A in the pathogenesis of fibrosis. |
| Databáze: | OpenAIRE |
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