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The survival and function of IL-10-producing regulatory B cells are negatively controlled by SLAMF5

Author

Listed:
  • Lihi Radomir

    (The Weizmann Institute of Science)

  • Matthias P. Kramer

    (The Weizmann Institute of Science)

  • Michal Perpinial

    (The Weizmann Institute of Science)

  • Nofar Schottlender

    (The Weizmann Institute of Science)

  • Stav Rabani

    (The Weizmann Institute of Science)

  • Keren David

    (The Weizmann Institute of Science)

  • Anna Wiener

    (The Weizmann Institute of Science)

  • Hadas Lewinsky

    (The Weizmann Institute of Science)

  • Shirly Becker-Herman

    (The Weizmann Institute of Science)

  • Rina Aharoni

    (The Weizmann Institute of Science)

  • Ron Milo

    (Barzilai University Medical Center
    Ben-Gurion University of the Negev)

  • Claudia Mauri

    (University College London)

  • Idit Shachar

    (The Weizmann Institute of Science)

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.

Suggested Citation

  • Lihi Radomir & Matthias P. Kramer & Michal Perpinial & Nofar Schottlender & Stav Rabani & Keren David & Anna Wiener & Hadas Lewinsky & Shirly Becker-Herman & Rina Aharoni & Ron Milo & Claudia Mauri & , 2021. "The survival and function of IL-10-producing regulatory B cells are negatively controlled by SLAMF5," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
  • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-22230-z
    DOI: 10.1038/s41467-021-22230-z
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    Cited by:

    1. Juan F. Quintana & Praveena Chandrasegaran & Matthew C. Sinton & Emma M. Briggs & Thomas D. Otto & Rhiannon Heslop & Calum Bentley-Abbot & Colin Loney & Luis de Lecea & Neil A. Mabbott & Annette MacLe, 2022. "Single cell and spatial transcriptomic analyses reveal microglia-plasma cell crosstalk in the brain during Trypanosoma brucei infection," Nature Communications, Nature, vol. 13(1), pages 1-19, December.

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