PloS one, 2014-08, Vol.9 (8), p.e105351-e105351
2014
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Details
- Autor(en) / Beteiligte
- Titel
- Differential modulation by IL-17A of Cholangitis versus Colitis in IL-2Rα deleted mice
- Ist Teil von
- PloS one, 2014-08, Vol.9 (8), p.e105351-e105351
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2014
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0105351Titel-ID: cdi_plos_journals_1554274732
- Format
- –
- Schlagworte
- Animals, Autoimmunity, Biology and Life Sciences, CD4 antigen, CD8 antigen, CD8-Positive T-Lymphocytes - metabolism, Cholangitis, Cholangitis - genetics, Cholangitis - metabolism, Chronic illnesses, Cirrhosis, Clonal deletion, Colitis, Colitis - genetics, Colitis - metabolism, Colon, Cytokines, Helper cells, Hepatitis, Hepatocytes, Hepatology, Immunology, Inflammation, Inflammatory bowel disease, Inflammatory bowel diseases, Inflammatory response, Interferon, Interleukin, Interleukin 2 receptors, Interleukin-17 - deficiency, Interleukin-17 - genetics, Interleukin-17 - metabolism, Interleukin-2 Receptor alpha Subunit - deficiency, Interleukin-2 Receptor alpha Subunit - genetics, Interleukin-2 Receptor alpha Subunit - metabolism, Intestine, Laboratories, Life sciences, Liver, Liver cirrhosis, Liver diseases, Lymphocytes, Lymphocytes T, Medicine and Health Sciences, Mice, Mice, Knockout, Natural killer cells, Pathogenesis, Pathology, Pharmaceutical sciences, Primary biliary cirrhosis, Rheumatoid arthritis, Rheumatology, Rodents, γ-Interferon