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

Nature Communications
Sunglim ChoLi-Fan Lu

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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Citations

Mar 16, 2019·Immunological Reviews·Julia MaulDirk Baumjohann
Mar 5, 2020·Cellular and Molecular Life Sciences : CMLS·Shrikanth C Basavarajappa, Parameswaran Ramakrishnan
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Sep 23, 2021·Immunological Reviews·Sunglim ChoLi-Fan Lu

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Datasets Mentioned

BETA
GSE113975

Methods Mentioned

BETA
RNA-seq
PCR
FACS
Assay
ELISA
transfection

Software Mentioned

ARRIVE
HOMER
Image J
GESA
FlowJo
Gene Set Enrichment Analysis ( GSEA
GSEA

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