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Adenosine receptor 2a agonists target mouse CD11c+T-bet+ B cells in infection and autoimmunity

Author

Listed:
  • Russell C. Levack

    (Upstate Medical University
    University of Pittsburgh School of Medicine)

  • Krista L. Newell

    (Upstate Medical University)

  • Berenice Cabrera-Martinez

    (Upstate Medical University)

  • Justin Cox

    (Upstate Medical University)

  • Andras Perl

    (Upstate Medical University)

  • Sheldon I. Bastacky

    (University of Pittsburgh School of Medicine)

  • Gary M. Winslow

    (Upstate Medical University)

Abstract

CD11c+T-bet+ B cells are recognized as an important component of humoral immunity and autoimmunity. These cells can be distinguished from other B cells by their higher expression of the adenosine receptor 2a. Here we address whether A2A receptor activation can affect CD11c+T-bet+ B cells. We show that administration of the A2A receptor agonist CGS-21680 depletes established CD11c+T-bet+ B cells in ehrlichial-infected mice, in a B cell-intrinsic manner. Agonist treatment similarly depletes CD11c+T-bet+ B cells and CD138+ B cells and reduces anti-nuclear antibodies in lupus-prone mice. Agonist treatment is also associated with reduced kidney pathology and lymphadenopathy. Moreover, A2A receptor stimulation depletes pathogenic lymphocytes and ameliorates disease even after disease onset, highlighting the therapeutic potential of this treatment. This study suggests that targeting the adenosine signaling pathway may provide a method for the treatment of lupus and other autoimmune diseases mediated by T-bet+ B cells.

Suggested Citation

  • Russell C. Levack & Krista L. Newell & Berenice Cabrera-Martinez & Justin Cox & Andras Perl & Sheldon I. Bastacky & Gary M. Winslow, 2022. "Adenosine receptor 2a agonists target mouse CD11c+T-bet+ B cells in infection and autoimmunity," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28086-1
    DOI: 10.1038/s41467-022-28086-1
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    References listed on IDEAS

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    1. Shu Wang & Jingya Wang & Varsha Kumar & Jodi L. Karnell & Brian Naiman & Phillip S. Gross & Saifur Rahman & Kamelia Zerrouki & Richard Hanna & Christopher Morehouse & Nicholas Holoweckyj & Hao Liu & Z, 2018. "IL-21 drives expansion and plasma cell differentiation of autoreactive CD11chiT-bet+ B cells in SLE," Nature Communications, Nature, vol. 9(1), pages 1-14, December.
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