CD4+ T-cell-derived IL-10 promotes CNS inflammation in mice by sustaining effector T cell survival
Nir Yogev, Tanja Bedke, Yasushi Kobayashi, Leonie Brockmann, Dominika Lukas, Tommy Regen, Andrew L. Croxford, Alexei Nikolav, Nadine Hövelmeyer, Esther von Stebut, Marco Prinz, Carles Úbeda, Kevin J. Maloy, Nicola Gagliani, Richard A. Flavell, Ari Waisman, Samuel Huber
Abstract
Interleukin (IL)-10 is considered a prototypical anti-inflammatory cytokine, significantly contributing to the maintenance and reestablishment of immune homeostasis. Accordingly, it has been shown in the intestine that IL-10 produced by Tregs can act on effector T cells, thereby limiting inflammation. Herein, we investigate whether this role also applies to IL-10 produced by T cells during central nervous system (CNS) inflammation. During neuroinflammation, both CNS-resident and -infiltrating cells produce IL-10; yet, as IL-10 has a pleotropic function, the exact contribution of the different cellular sources is not fully understood. We find that T-cell-derived IL-10, but not other relevant IL-10 sources, can promote inflammation in experimental autoimmune encephalomyelitis. Furthermore, in the CNS, T-cell-derived IL-10 acts on effector T cells, promoting their survival and thereby enhancing inflammation and CNS autoimmunity. Our data indicate a pro-inflammatory role of T-cell-derived IL-10 in the CNS.