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. 2021 Nov 16;12:761450. doi: 10.3389/fimmu.2021.761450

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Copyright © 2021 Casali, Li, Morales, Daw, Chupp, Fisher and Zan

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Epigenetic regulation of CSR to IgA by miR-146a. miR-146a targets the 3’UTRs of Smad2, Smad3 and Smad4 mRNAs to downregulate the expression of Smad2, Smad3 and Smad4, and reduce germline Iα-Cα transcription leading to a decreased CSR to IgA and IgA production. In B cells stimulation by TGF-β, activated Smad proteins lead to miR-146 reduction, which results in enhancement of expression of Smad proteins themselves. This miR-146a/Smad loop can amplify TGF-β-induced Smads promotion of CSR to IgA.