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| Content Provider | PubMed Central |
|---|---|
| Author | Yang, Wei Yao, Yuan Yang, Yan-qing Lu, Fang-ting Li, Liang Wang, Yin-hu Nakajima, Takahiko Tsuneyama, Koichi Ridgway, William M. Gershwin, M. Eric Lian, Zhe-xiong |
| Editor | Boone, David L. |
| Copyright Year | 2014 |
| Abstract | IFN-γ is a signature Th1 cell associated cytokine critical for the inflammatory response in autoimmunity with both pro-inflammatory and potentially protective functions. IL-17A is the hallmark of T helper 17 (Th17) cell subsets, produced by γδT, CD8+ T, NK and NKT cells. We have taken advantage of our colony of IL-2Rα−/− mice that spontaneously develop both autoimmune cholangitis and inflammatory bowel disease. In this model CD8+ T cells mediate biliary ductular damage, whereas CD4+ T cells mediate induction of colon-specific autoimmunity. Importantly, IL-2Rα−/− mice have high levels of interferon γ (IFN-γ), and interleukin-17A (IL-17A). We produced unique double deletions of mice that were either IL-17A−/−IL-2Rα−/− or IFN-γ−/−IL-2Rα−/− to specifically address the precise role of these two cytokines in the natural history of autoimmune cholangitis and colitis. Of note, deletion of IL-17A in IL-2Rα−/− mice led to more severe liver inflammation, but ameliorated colitis. In contrast, there were no significant changes in the immunopathology of double knock-out IFN-γ−/− IL-2Rα−/− mice, compared to single knock-out IL-2Rα−/− mice with respect to cholangitis or colitis. Furthermore, there was a significant increase in pathogenetic CD8+ T cells in the liver of IL-17A−/−IL-2Rα−/− mice. Our data suggest that while IL-17A plays a protective role in autoimmune cholangitis, it has a pro-inflammatory role in inflammatory bowel disease. These data take on particular significance in the potential use of anti-IL-17A therapy in humans with primary biliary cirrhosis. |
| Related Links | http://dx.doi.org/10.1371/journal.pone.0105351 |
| Starting Page | 105351 |
| File Format | |
| ISSN | 19326203 |
| e-ISSN | 19326203 |
| Journal | PLoS ONE |
| Issue Number | 8 |
| Volume Number | 9 |
| Language | English |
| Publisher | Public Library of Science |
| Publisher Date | 2014-08-01 |
| Access Restriction | Open |
| Rights Holder | Public Library of Science |
| Subject Keyword | Biochemistry, Genetics and Molecular Biology(all) Agricultural and Biological Sciences(all) Medicine(all) Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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