The interleukin-15 system suppresses T cell-mediated autoimmunity by regulating negative selection and nTH17 cell homeostasis in the thymus. (January 2015)

• Record Type: Journal Article
• Authors: Hou, Mau-Sheng; Huang, Shih-Ting; Tsai, Ming-Han; Yen, Ching-Cheng; Lai, Yein-Gei; Liou, Yae-Huei; Lin, Chih-Kung; Liao, Nan-Shih
• Is Part Of: Journal of autoimmunity. Volume 56(2015)
• Page Start: 118
• Page End: 129
• Publication Date: 2015-01
• Subjects: IL-15 -- IL-15Rα -- Thymus -- Negative selection -- nTH17; Autoimmunity -- Periodicals; Autoimmune diseases -- Periodicals; Autoantibodies -- Periodicals; Autoimmune Diseases -- Periodicals; Auto-immunité -- Périodiques; Maladies auto-immunes -- Périodiques; Electronic journals; 616.978005
• DOI: 10.1016/j.jaut.2014.11.003
• Languages: English
• ISSNs: 0896-8411

Abstract

Abstract: The interleukin-15 (IL-15) system is important for regulating both innate and adaptive immune responses, however, its role in autoimmune disease remained unclear. Here we found that Il15 −/− and Il15ra −/− mice spontaneously developed late-onset autoimmune phenotypes. CD4 + T cells of the knockout mice showed elevated autoreactivity as demonstrated by the induction of lymphocyte infiltration in the lacrimal and salivary glands when transferred into nude mice. The antigen-presenting cells in the thymic medullary regions expressed IL-15 and IL-15Rα, whose deficiency resulted in insufficient negative selection and elevated number of natural IL-17A-producing CD4 + thymocytes. These findings reveal previously unknown functions of the IL-15 system in thymocyte development, and thus a new layer of regulation in T cell-mediated autoimmunity. Highlights: Aged Il15ra −/− and Il15 −/− mice spontaneously developed autoimmune phenotypes. CD4 + T cells of Il15ra −/− and Il15 −/− mice showed elevated auto-reactivity. Thymic IL-15 system regulated thymocyte negative selection and nTH 17 development.