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. 2019 Apr 17;10:799. doi: 10.3389/fimmu.2019.00799

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Copyright © 2019 Curtale, Rubino and Locati.

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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Pervasive regulation of TLR signaling pathway by miR-146a/b family and miR-125a~99b~let-7e cluster. (A) During overt inflammation binding of LPS to TLR4 induces the expression of NF-κB pathway, that ultimately leads to the release of pro-inflammatory cytokines (including TNFα, IL-6, CCL3, and IL-12). NF-κB also positively regulates the expression of miR-146a, which operates a negative feedback control of the NF-κB-dependent inflammatory response by repressing TRAF-6 and IRAK1. (B) During the late phase of the inflammatory response, production of IL-10 induces the expression of miR-146b and miR-125a~99b~let-7e cluster, via STAT3 binding to their promoters, thus resulting into downregulation of multiple components of TLR signaling pathway.