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.

Details

Title
Differential cell-intrinsic regulations of germinal center B and T cells by miR-146a and miR-146b
Author
Cho, Sunglim 1   VIAFID ORCID Logo  ; Hyang-Mi, Lee 1 ; I-Shing, Yu 2   VIAFID ORCID Logo  ; Choi, Youn Soo 3 ; Hsi-Yuan, Huang 4 ; Somaye Sadat Hashemifar 5 ; Ling-Li, Lin 1 ; Mei-Chi, Chen 1 ; Afanasiev, Nikita D 1 ; Aly Azeem Khan 5 ; Lin, Shu-Wha 6 ; Rudensky, Alexander Y 7 ; Crotty, Shane 8   VIAFID ORCID Logo  ; Li-Fan, Lu 9   VIAFID ORCID Logo 

 Division of Biological Sciences, University of California, La Jolla, San Diego, CA, USA 
 Laboratory Animal Center, College of Medicine, National Taiwan University, Taipei, Taiwan 
 Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA; Department of Medicine, College of Medicine, Seoul National University, Seoul, Korea 
 Department of Laboratory Medicine, China Medical University Hospital, China Medical University, Taichung, Taiwan 
 Toyota Technological Institute, Chicago, IL, USA 
 Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan; Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan 
 Howard Hughes Medical Institute and Immunology Program, Ludwig Center at Memorial Sloan-Kettering Cancer Center, Memorial Sloan-Kettering Cancer Center, New York, NY, USA 
 Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA; Division of Infectious Diseases, Department of Medicine, University of California, La Jolla, San Diego, CA, USA 
 Division of Biological Sciences, University of California, La Jolla, San Diego, CA, USA; Moores Cancer Center, University of California, La Jolla, San Diego, CA, USA; Center for Microbiome Innovation, University of California, La Jolla, San Diego, CA, USA 
Pages
1-13
Publication year
2018
Publication date
Jul 2018
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2070787607
Copyright
© 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.