CD4+ T-cell-derived IL-10 promotes CNS inflammation in mice by sustaining effector T cell survival.

Cell reports 2022 Mar 29

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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. Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.

Citation

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 Ubeda, Kevin J Maloy, Nicola Gagliani, Richard A Flavell, Ari Waisman, Samuel Huber. CD4+ T-cell-derived IL-10 promotes CNS inflammation in mice by sustaining effector T cell survival. Cell reports. 2022 Mar 29;38(13):110565