Radomir, L;
Kramer, MP;
Perpinial, M;
Schottlender, N;
Rabani, S;
David, K;
Wiener, A;
... Shachar, I; + view all
(2021)
The survival and function of IL-10-producing regulatory B cells are negatively controlled by SLAMF5.
Nature Communications
, 12
(1)
, Article 1893. 10.1038/s41467-021-22230-z.
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Abstract
B cells have essential functions in multiple sclerosis and in its mouse model, experimental autoimmune encephalomyelitis, both as drivers and suppressors of the disease. The suppressive effects are driven by a regulatory B cell (Breg) population that functions, primarily but not exclusively, via the production of IL-10. However, the mechanisms modulating IL-10-producing Breg abundance are poorly understood. Here we identify SLAMF5 for controlling IL-10+ Breg maintenance and function. In EAE, the deficiency of SLAMF5 in B cells causes accumulation of IL10+ Bregs in the central nervous system and periphery. Blocking SLAMF5 in vitro induces both human and mouse IL-10-producing Breg cells and increases their survival with a concomitant increase of a transcription factor, c-Maf. Finally, in vivo SLAMF5 blocking in EAE elevates IL-10+ Breg levels and ameliorates disease severity. Our results suggest that SLAMF5 is a negative moderator of IL-10+ Breg cells, and may serve as a therapeutic target in MS and other autoimmune diseases.
| Type: | Article |
|---|---|
| Title: | The survival and function of IL-10-producing regulatory B cells are negatively controlled by SLAMF5 |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/s41467-021-22230-z |
| Publisher version: | http://dx.doi.org/10.1038/s41467-021-22230-z |
| Language: | English |
| Additional information: | Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
| Keywords: | Animals, B-Lymphocytes, Regulatory, Cell Survival, Cells, Cultured, Disease Models, Animal, Encephalomyelitis, Autoimmune, Experimental, Humans, Interleukin-10, Mice, Mice, Inbred C57BL, Mice, Knockout, Multiple Sclerosis, Signaling Lymphocytic Activation Molecule Family |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10126151 |
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