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miR-146a controls the resolution of T cell responses in mice

Yang, Lili and Boldin, Mark P. and Yu, Yang and Liu, Claret Siyuan and Ea, Chee-Kwee and Ramakrishnan, Parameswaran and Taganov, Konstantin D. and Zhao, Jimmy L. and Baltimore, David (2012) miR-146a controls the resolution of T cell responses in mice. Journal of Experimental Medicine, 209 (9). pp. 1655-1670. ISSN 0022-1007. PMCID PMC3428948.

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T cell responses in mammals must be tightly regulated to both provide effective immune protection and avoid inflammation-induced pathology. NF-κB activation is a key signaling event induced by T cell receptor (TCR) stimulation. Dysregulation of NF-κB is associated with T cell–mediated inflammatory diseases and malignancies, highlighting the importance of negative feedback control of TCR-induced NF-κB activity. In this study we show that in mice, T cells lacking miR-146a are hyperactive in both acute antigenic responses and chronic inflammatory autoimmune responses. TCR-driven NF-κB activation up-regulates the expression of miR-146a, which in turn down-regulates NF-κB activity, at least partly through repressing the NF-κB signaling transducers TRAF6 and IRAK1. Thus, our results identify miR-146a as an important new member of the negative feedback loop that controls TCR signaling to NF-κB. Our findings also add microRNA to the list of regulators that control the resolution of T cell responses.

Item Type:Article
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URLURL TypeDescription DOIArticle CentralArticle
Boldin, Mark P.0000-0003-4593-0669
Ramakrishnan, Parameswaran0000-0002-1314-827X
Baltimore, David0000-0001-8723-8190
Additional Information:© 2012 Yang et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see After six months it is available under a Creative Commons License (Attribution– Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons. org/licenses/by-nc-sa/3.0/). Submitted: 19 October 2011. Accepted: 18 July 2012. We thank the California Institute of Technology animal facility for providing animal support, Shengli Hao for providing p50-/- mice, Pin Wang, Shengli Hao, and Michael Bethune for critical reading of this manuscript, and all members of the Baltimore group for insightful discussions. This work was supported by the National Institutes of Health P01 CA132681A and 5R01AI079243-02 grants. D. Baltimore is a director and chairman of the Scientific Advisory board of Regulus Therapeutics Inc., a biotech company developing miRNA-based drugs. Authors have no further conflicting interests.
Funding AgencyGrant Number
NIHP01 CA132681A
Issue or Number:9
PubMed Central ID:PMC3428948
Record Number:CaltechAUTHORS:20120910-071639316
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Official Citation:miR-146a controls the resolution of T cell responses in mice Lili Yang, Mark P. Boldin, Yang Yu, Claret Siyuan Liu, Chee-Kwee Ea, Parameswaran Ramakrishnan, Konstantin D. Taganov, Jimmy L. Zhao, and David Baltimore 209:1655-1670. doi:10.1084/jem.20112218
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:33949
Deposited By: Ruth Sustaita
Deposited On:10 Sep 2012 15:15
Last Modified:08 Jul 2020 22:03

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