Function of miR-146a in Controlling Treg Cell-Mediated Regulation of Th1 Responses

Li Fan Lu, Mark P. Boldin, Ashutosh Chaudhry, Ling Li Lin, Konstantin D. Taganov, Toshikatsu Hanada, Akihiko Yoshimura, David Baltimore, Alexander Y. Rudensky

Research output: Contribution to journalArticle

571 Citations (Scopus)

Abstract

Foxp3+ regulatory T (Treg) cells maintain immune homeostasis by limiting different types of inflammatory responses. Here, we report that miR-146a, one of the miRNAs prevalently expressed in Treg cells, is critical for their suppressor function. The deficiency of miR-146a in Treg cells resulted in a breakdown of immunological tolerance manifested in fatal IFNγ-dependent immune-mediated lesions in a variety of organs. This was likely due to augmented expression and activation of signal transducer and activator transcription 1 (Stat1), a direct target of miR-146a. Likewise, heightened Stat1 activation in Treg cells subjected to a selective ablation of SOCS1, a key negative regulator of Stat1 phosphorylation downstream of the IFNγ receptor, was associated with analogous Th1-mediated pathology. Our results suggest that specific aspects of Treg suppressor function are controlled by a single miRNA and that an optimal range of Stat1 activation is important for Treg-mediated control of Th1 responses and associated autoimmunity.

Original languageEnglish
Pages (from-to)914-929
Number of pages16
JournalCell
Volume142
Issue number6
DOIs
Publication statusPublished - 2010 Sep

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STAT1 Transcription Factor
Regulatory T-Lymphocytes
Chemical activation
MicroRNAs
Transcriptional Activation
Phosphorylation
Pathology
Ablation
Autoimmunity
Homeostasis

Keywords

  • Cellimmuno
  • Humdisease

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Lu, L. F., Boldin, M. P., Chaudhry, A., Lin, L. L., Taganov, K. D., Hanada, T., ... Rudensky, A. Y. (2010). Function of miR-146a in Controlling Treg Cell-Mediated Regulation of Th1 Responses. Cell, 142(6), 914-929. https://doi.org/10.1016/j.cell.2010.08.012

Function of miR-146a in Controlling Treg Cell-Mediated Regulation of Th1 Responses. / Lu, Li Fan; Boldin, Mark P.; Chaudhry, Ashutosh; Lin, Ling Li; Taganov, Konstantin D.; Hanada, Toshikatsu; Yoshimura, Akihiko; Baltimore, David; Rudensky, Alexander Y.

In: Cell, Vol. 142, No. 6, 09.2010, p. 914-929.

Research output: Contribution to journalArticle

Lu, LF, Boldin, MP, Chaudhry, A, Lin, LL, Taganov, KD, Hanada, T, Yoshimura, A, Baltimore, D & Rudensky, AY 2010, 'Function of miR-146a in Controlling Treg Cell-Mediated Regulation of Th1 Responses', Cell, vol. 142, no. 6, pp. 914-929. https://doi.org/10.1016/j.cell.2010.08.012
Lu LF, Boldin MP, Chaudhry A, Lin LL, Taganov KD, Hanada T et al. Function of miR-146a in Controlling Treg Cell-Mediated Regulation of Th1 Responses. Cell. 2010 Sep;142(6):914-929. https://doi.org/10.1016/j.cell.2010.08.012
Lu, Li Fan ; Boldin, Mark P. ; Chaudhry, Ashutosh ; Lin, Ling Li ; Taganov, Konstantin D. ; Hanada, Toshikatsu ; Yoshimura, Akihiko ; Baltimore, David ; Rudensky, Alexander Y. / Function of miR-146a in Controlling Treg Cell-Mediated Regulation of Th1 Responses. In: Cell. 2010 ; Vol. 142, No. 6. pp. 914-929.
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