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Differential cell-intrinsic regulations of germinal center B and T cells by miR-146a and miR-146b.

Sunglim Cho | Hyang-Mi Lee | I-Shing Yu | Youn Soo Choi | Hsi-Yuan Huang | Somaye Sadat Hashemifar | Ling-Li Lin | Mei-Chi Chen | Nikita D Afanasiev | Aly Azeem Khan | Shu-Wha Lin | Alexander Y Rudensky | Shane Crotty | Li-Fan Lu
Nature communications | 2018

Reciprocal interactions between B and follicular T helper (Tfh) cells orchestrate the germinal center (GC) reaction, a hallmark of humoral immunity. Abnormal GC responses could lead to the production of pathogenic autoantibodies and the development of autoimmunity. Here we show that miR-146a controls GC responses by targeting multiple CD40 signaling pathway components in B cells; by contrast, loss of miR-146a in T cells does not alter humoral responses. However, specific deletion of both miR-146a and its paralog, miR-146b, in T cells increases Tfh cell numbers and enhanced GC reactions. Thus, our data reveal differential cell-intrinsic regulations of GC B and Tfh cells by miR-146a and miR-146b. Together, members of the miR-146 family serve as crucial molecular brakes to coordinately control GC reactions to generate protective humoral responses without eliciting unwanted autoimmunity.

Pubmed ID: 30013024

Associated grants

  • Agency: U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID), International
    Id: AI089935
  • Agency: U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID), International
    Id: AI108651
  • Agency: NIAID NIH HHS, United States
    Id: R01 AI108651
  • Agency: U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID), International
    Id: AI123782
  • Agency: NIAID NIH HHS, United States
    Id: K99 AI089935
  • Agency: NIAID NIH HHS, United States
    Id: R00 AI089935
  • Agency: U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID), International
    Id: AI103646
  • Agency: NCI NIH HHS, United States
    Id: P30 CA008748
  • Agency: NIAID NIH HHS, United States
    Id: R21 AI103646
  • Agency: NIAID NIH HHS, United States
    Id: R21 AI123782

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