1. Endogenous interleukin-22 protects against inflammatory bowel disease but not autoimmune cholangitis in dominant negative form of transforming growth factor beta receptor type II mice
- Author
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Christopher L. Bowlus, Patrick S.C. Leung, Weici Zhang, William M. Ridgway, Xiao-Song He, G.-X. Yang, Ying Sun, M. E. Gershwin, Aftab A. Ansari, and Koichi Tsuneyama
- Subjects
0301 basic medicine ,Cholangitis ,Immunology ,Inflammation ,medicine.disease_cause ,Interleukin-23 ,Inflammatory bowel disease ,Autoimmune Diseases ,Autoimmunity ,Mice ,03 medical and health sciences ,medicine ,Interleukin 23 ,Animals ,Immunology and Allergy ,Mice, Knockout ,Autoimmune disease ,biology ,Liver Cirrhosis, Biliary ,business.industry ,Interleukins ,Interleukin-17 ,Interleukin ,Original Articles ,Transforming growth factor beta ,Inflammatory Bowel Diseases ,medicine.disease ,Mice, Inbred C57BL ,Disease Models, Animal ,030104 developmental biology ,biology.protein ,Cytokines ,Interleukin 17 ,medicine.symptom ,business ,Receptors, Transforming Growth Factor beta - Abstract
Summary During chronic inflammation, interleukin (IL)-22 expression is up-regulated in both CD4 and CD8 T cells, exerting a protective role in infections. However, in autoimmunity, IL-22 appears to have either a protective or a pathogenic role in a variety of murine models of autoimmunity and, by extrapolation, in humans. It is not clear whether IL-22 itself mediates inflammation or is a by-product of inflammation. We have taken advantage of the dominant negative form of transforming growth factor beta receptor type II (dnTGF-βRII) mice that develop both inflammatory bowel disease and autoimmune cholangitis and studied the role and the biological function of IL-22 by generating IL-22–/– dnTGF-βRII mice. Our data suggest that the influence of IL-22 on autoimmunity is determined in part by the local microenvironment. In particular, IL-22 deficiency exacerbates tissue injury in inflammatory bowel disease, but has no influence on either the hepatocytes or cholangiocytes in the same model. These data take on particular significance in the previously defined effects of IL-17A, IL-12p40 and IL-23p19 deficiency and emphasize that, in colitis, there is a dominant role of IL-23/T helper type 17 (Th17) signalling. Furthermore, the levels of IL-22 are IL-23-dependent. The use of cytokine therapy in patients with autoimmune disease has significant potential, but must take into account the overlapping and often promiscuous effects that can theoretically exacerbate inflammation.
- Published
- 2016