| First Author | Yang W | Year | 2014 |
| Journal | PLoS One | Volume | 9 |
| Issue | 8 | Pages | e105351 |
| PubMed ID | 25133396 | Mgi Jnum | J:223143 |
| Mgi Id | MGI:5648131 | Doi | 10.1371/journal.pone.0105351 |
| Citation | Yang W, et al. (2014) Differential modulation by IL-17A of Cholangitis versus Colitis in IL-2Ralpha deleted mice. PLoS One 9(8):e105351 |
| abstractText | IFN-gamma 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 gammadeltaT, CD8+ T, NK and NKT cells. We have taken advantage of our colony of IL-2Ralpha-/- 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-2Ralpha-/- mice have high levels of interferon gamma (IFN-gamma), and interleukin-17A (IL-17A). We produced unique double deletions of mice that were either IL-17A-/-IL-2Ralpha-/- or IFN-gamma-/-IL-2Ralpha-/- 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-2Ralpha-/- 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-gamma-/- IL-2Ralpha-/- mice, compared to single knock-out IL-2Ralpha-/- 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-2Ralpha-/- 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. |
