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 journalArticle

171 Citations (Scopus)

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 1 2012

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T-Cell Antigen Receptor
T-Lymphocytes
TNF Receptor-Associated Factor 6
Transducers
MicroRNAs
Autoimmunity
Mammals
Up-Regulation
Down-Regulation
Pathology
Inflammation
Neoplasms

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Yang, L., Boldin, M. P., Yu, Y., Liu, C. S., Ea, C. K., Ramakrishnan, P., ... Baltimore, D. (2012). miR-146a controls the resolution of T cell responses in mice. Journal of Experimental Medicine, 209(9), 1655-1670. https://doi.org/10.1084/jem.20112218

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.

In: Journal of Experimental Medicine, Vol. 209, No. 9, 01.08.2012, p. 1655-1670.

Research output: Contribution to journalArticle

Yang, L, Boldin, MP, Yu, Y, Liu, CS, Ea, CK, Ramakrishnan, P, Taganov, KD, Zhao, JL & Baltimore, D 2012, 'miR-146a controls the resolution of T cell responses in mice', Journal of Experimental Medicine, vol. 209, no. 9, pp. 1655-1670. https://doi.org/10.1084/jem.20112218
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. In: Journal of Experimental Medicine. 2012 ; Vol. 209, No. 9. pp. 1655-1670.
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