Bleomycin and IL-1β–mediated Pulmonary Fibrosis is IL-17A Dependent
| Title: | Bleomycin and IL-1β–mediated Pulmonary Fibrosis is IL-17A Dependent |
| Author: |
Wilson, Mark S.; Madala, Satish K.; Ramalingam, Thirumalai R.; Gochuico, Bernadette R.; Cheever, Allen W.; Wynn, Thomas A.; Rosas, Ivan O.
Note: Order does not necessarily reflect citation order of authors. |
| Citation: | Wilson, Mark S., Satish K. Madala, Thirumalai R. Ramalingam, Bernadette R. Gochuico, Ivan O. Rosas, Allen W. Cheever, and Thomas A. Wynn. 2010. Bleomycin and IL-1β- mediated pulmonary fibrosis is IL-17A dependent. The Journal of Experimental Medicine 207(3): 535-552. |
| Full Text & Related Files: |
2839145.pdf (7.741Mb; PDF) 
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| Abstract: | Idiopathic pulmonary fibrosis (IPF) is a destructive inflammatory disease with limited therapeutic options. To better understand the inflammatory responses that precede and concur with collagen deposition, we used three models of pulmonary fibrosis and identify a critical mechanistic role for IL-17A. After exposure to bleomycin (BLM), but not Schistosoma mansoni eggs, IL-17A produced by CD4\(^+\) and γδ\(^+\) T cells induced significant neutrophilia and pulmonary fibrosis. Studies conducted with C57BL/6 \(il17a^{−/−}\) mice confirmed an essential role for IL-17A. Mechanistically, using \(ifnγ^{−/−}, il10^{−/−}, il10^{−/−}il12p40^{−/−}\), and \(il10^{−/−}il17a^{−/−}\) mice and TGF-β blockade, we demonstrate that IL-17A–driven fibrosis is suppressed by IL-10 and facilitated by IFN-γ and IL-12/23p40. BLM-induced IL-17A production was also TGF-β dependent, and recombinant IL-17A–mediated fibrosis required TGF-β, suggesting cooperative roles for IL-17A and TGF-β in the development of fibrosis. Finally, we show that fibrosis induced by IL-1β, which mimics BLM-induced fibrosis, is also highly dependent on IL-17A. IL-17A and IL-1β were also increased in the bronchoalveolar lavage fluid of patients with IPF. Together, these studies identify a critical role for IL-17A in fibrosis, illustrating the potential utility of targeting IL-17A in the treatment of drug and inflammation-induced fibrosis. |
| Published Version: | doi:10.1084/jem.20092121 |
| Other Sources: | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2839145/pdf/ |
| Terms of Use: | This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA |
| Citable link to this page: | http://nrs.harvard.edu/urn-3:HUL.InstRepos:5343416 |
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