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The survival and function of IL-10-producing regulatory B cells are negatively controlled by SLAMF5
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...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994628/ https://www.ncbi.nlm.nih.gov/pubmed/33767202 http://dx.doi.org/10.1038/s41467-021-22230-z |
Sumario: | 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. |
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