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

Yogev, N. et al. (2022) CD4+ T-cell-derived IL-10 promotes CNS inflammation in mice by sustaining effector T cell survival. Cell Reports, 38(13), 110565. (doi: 10.1016/j.celrep.2022.110565) (PMID:35354043)

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.

• Item Type: Articles
• Additional Information: This work was supported, in part, by the Deutsche Forschungsgemeinschaft (DFG) grants HU 1714/7-1 and HU 1714/10-1 to S.H., TRR 128/3 and TRR156 (246807620) to A.W., CRC1292 to A.W. and E.v.S., and GA 2441/3-1 to N.G., as well as a Center for Molecular Medicine, Cologne, research grant to N.Y. S.H. has an endowed Heisenberg-Professorship awarded by the DFG. K.J.M. is funded by Wellcome Trust Investigator Award 102972. PID2020-120292RB-I00 from MICINN to C.U.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Maloy, Professor Kevin
• Authors: Yogev, N., Bedke, T., Kobayashi, Y., Brockmann, L., Lukas, D., Regen, T., Croxford, A. L., Nikolav, A., Hövelmeyer, N., von Stebut, E., Prinz, M., Ubeda, C., Maloy, K. J., Gagliani, N., Flavell, R. A., Waisman, A., and Huber, S.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Research Centre: College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Immunobiology
• Journal Name: Cell Reports
• Publisher: Elsevier (Cell Press)
• ISSN: 2211-1247
• ISSN (Online): 2211-1247
• Copyright Holders: Copyright © 2022 The Authors
• First Published: First published in Cell Reports 38(13): 110565
• Publisher Policy: Reproduced under a Creative Commons License

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
313264		Regulation of intestinal immune homeostasis by NOD-like receptors	Kevin Maloy	Wellcome Trust (WELLCOTR)	102972/A/13/Z	III - Immunology