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

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 d...

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Autores principales: Yang, Lili, Boldin, Mark P., Yu, Yang, Liu, Claret Siyuan, Ea, Chee-Kwee, Ramakrishnan, Parameswaran, Taganov, Konstantin D., Zhao, Jimmy L., Baltimore, David
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3428948/
https://www.ncbi.nlm.nih.gov/pubmed/22891274
http://dx.doi.org/10.1084/jem.20112218
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author Yang, Lili
Boldin, Mark P.
Yu, Yang
Liu, Claret Siyuan
Ea, Chee-Kwee
Ramakrishnan, Parameswaran
Taganov, Konstantin D.
Zhao, Jimmy L.
Baltimore, David
author_facet Yang, Lili
Boldin, Mark P.
Yu, Yang
Liu, Claret Siyuan
Ea, Chee-Kwee
Ramakrishnan, Parameswaran
Taganov, Konstantin D.
Zhao, Jimmy L.
Baltimore, David
author_sort Yang, Lili
collection PubMed
description 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.
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spelling pubmed-34289482013-02-27 miR-146a controls the resolution of T cell responses in mice Yang, Lili Boldin, Mark P. Yu, Yang Liu, Claret Siyuan Ea, Chee-Kwee Ramakrishnan, Parameswaran Taganov, Konstantin D. Zhao, Jimmy L. Baltimore, David J Exp Med Article 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. The Rockefeller University Press 2012-08-27 /pmc/articles/PMC3428948/ /pubmed/22891274 http://dx.doi.org/10.1084/jem.20112218 Text en © 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 http://www.rupress.org/terms). 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/).
spellingShingle Article
Yang, Lili
Boldin, Mark P.
Yu, Yang
Liu, Claret Siyuan
Ea, Chee-Kwee
Ramakrishnan, Parameswaran
Taganov, Konstantin D.
Zhao, Jimmy L.
Baltimore, David
miR-146a controls the resolution of T cell responses in mice
title miR-146a controls the resolution of T cell responses in mice
title_full miR-146a controls the resolution of T cell responses in mice
title_fullStr miR-146a controls the resolution of T cell responses in mice
title_full_unstemmed miR-146a controls the resolution of T cell responses in mice
title_short miR-146a controls the resolution of T cell responses in mice
title_sort mir-146a controls the resolution of t cell responses in mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3428948/
https://www.ncbi.nlm.nih.gov/pubmed/22891274
http://dx.doi.org/10.1084/jem.20112218
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