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 journalArticlepeer-review

797 Citations (Scopus)


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
Issue number6
Publication statusPublished - 2010 Sept


  • Cellimmuno
  • Humdisease

ASJC Scopus subject areas

  • General Biochemistry,Genetics and Molecular Biology


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