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, David Baltimore

Research output: Contribution to journalArticlepeer-review

196 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1655-1670
Number of pages16
JournalJournal of Experimental Medicine
Volume209
Issue number9
DOIs
StatePublished - Aug 2012

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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