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

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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 1

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Keywords

  • Cellimmuno
  • Humdisease

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Lu, L. F., Boldin, M. P., Chaudhry, A., Lin, L. L., Taganov, K. D., Hanada, T., Yoshimura, A., Baltimore, D., & 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