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Low-dose IL-2 enhances the generation of IL-10-producing immunoregulatory B cells

Author

Listed:
  • Akimichi Inaba

    (University of Cambridge Department of Medicine)

  • Zewen Kelvin Tuong

    (University of Cambridge Department of Medicine
    Wellcome Sanger Institute)

  • Tian X. Zhao

    (Division of Cardiovascular Medicine, University of Cambridge)

  • Andrew P. Stewart

    (University of Cambridge Department of Medicine)

  • Rebeccah Mathews

    (University of Cambridge Department of Medicine)

  • Lucy Truman

    (West Suffolk Hospital)

  • Rouchelle Sriranjan

    (University of Cambridge)

  • Jane Kennet

    (University of Cambridge)

  • Kourosh Saeb-Parsy

    (University of Cambridge
    National Institute for Health Research Cambridge Biomedical Research Centre)

  • Linda Wicker

    (University of Oxford)

  • Frank Waldron-Lynch

    (Novartis Institutes for BioMedical Research, Autoimmunity Transplantation Inflammation)

  • Joseph Cheriyan

    (University of Cambridge)

  • John A. Todd

    (University of Oxford)

  • Ziad Mallat

    (Division of Cardiovascular Medicine, University of Cambridge
    Universite de Paris and INSERM)

  • Menna R. Clatworthy

    (University of Cambridge Department of Medicine
    Wellcome Sanger Institute)

Abstract

Dysfunction of interleukin-10 producing regulatory B cells has been associated with the pathogenesis of autoimmune diseases, but whether regulatory B cells can be therapeutically induced in humans is currently unknown. Here we demonstrate that a subset of activated B cells expresses CD25, and the addition of low-dose recombinant IL-2 to in vitro stimulated peripheral blood and splenic human B cells augments IL-10 secretion. Administration of low dose IL-2, aldesleukin, to patients increases IL-10-producing B cells. Single-cell RNA sequencing of circulating immune cells isolated from low dose IL2-treated patients reveals an increase in plasmablast and plasma cell populations that are enriched for a regulatory B cell gene signature. The transcriptional repressor BACH2 is significantly down-regulated in plasma cells from IL-2-treated patients, BACH2 binds to the IL-10 gene promoter, and Bach2 depletion or genetic deficiency increases B cell IL-10, implicating BACH2 suppression as an important mechanism by which IL-2 may promote an immunoregulatory phenotype in B cells.

Suggested Citation

  • Akimichi Inaba & Zewen Kelvin Tuong & Tian X. Zhao & Andrew P. Stewart & Rebeccah Mathews & Lucy Truman & Rouchelle Sriranjan & Jane Kennet & Kourosh Saeb-Parsy & Linda Wicker & Frank Waldron-Lynch & , 2023. "Low-dose IL-2 enhances the generation of IL-10-producing immunoregulatory B cells," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-37424-w
    DOI: 10.1038/s41467-023-37424-w
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    1. Dorin-Mirel Popescu & Rachel A. Botting & Emily Stephenson & Kile Green & Simone Webb & Laura Jardine & Emily F. Calderbank & Krzysztof Polanski & Issac Goh & Mirjana Efremova & Meghan Acres & Daniel , 2019. "Decoding human fetal liver haematopoiesis," Nature, Nature, vol. 574(7778), pages 365-371, October.
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