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

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

  • Nat Commun. 2018 Jul 16;9(1):2757. doi: 10.1038/s41467-018-05196-3.
Sunglim Cho 1,  Hyang-Mi Lee 1,  I-Shing Yu 2,  Youn Soo Choi 3 4,  Hsi-Yuan Huang 5,  Somaye Sadat Hashemifar 6,  Ling-Li Lin 1,  Mei-Chi Chen 1,  Nikita D Afanasiev 1,  Aly Azeem Khan 6,  Shu-Wha Lin 7 8,  Alexander Y Rudensky 9,  Shane Crotty 3 10,  Li-Fan Lu 11 12 13
Affiliations

Affiliations

  • 1 Division of Biological Sciences, University of California, La Jolla, San Diego, CA, 92093, USA.
  • 2 Laboratory Animal Center, College of Medicine, National Taiwan University, Taipei, 100, Taiwan.
  • 3 Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA, 92037, USA.
  • 4 Department of Medicine, College of Medicine, Seoul National University, Seoul, 03080, Korea.
  • 5 Department of Laboratory Medicine, China Medical University Hospital, China Medical University, Taichung, Taiwan.
  • 6 Toyota Technological Institute, Chicago, IL, 60637, USA.
  • 7 Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, 100, Taiwan.
  • 8 Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, 100, Taiwan.
  • 9 Howard Hughes Medical Institute and Immunology Program, Ludwig Center at Memorial Sloan-Kettering Cancer Center, Memorial Sloan-Kettering Cancer Center, New York, NY, 10065, USA.
  • 10 Division of Infectious Diseases, Department of Medicine, University of California, La Jolla, San Diego, CA, 92037, USA.
  • 11 Division of Biological Sciences, University of California, La Jolla, San Diego, CA, 92093, USA. [email protected].
  • 12 Moores Cancer Center, University of California, La Jolla, San Diego, CA, 92093, USA. [email protected].
  • 13 Center for Microbiome Innovation, University of California, La Jolla, San Diego, CA, 92093, USA. [email protected].
PMID: 30013024 DOI: 10.1038/s41467-018-05196-3
Abstract

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.

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