[HTML][HTML] Function of miR-146a in controlling Treg cell-mediated regulation of Th1 responses

LF Lu, MP Boldin, A Chaudhry, LL Lin, KD Taganov… - Cell, 2010 - cell.com
LF Lu, MP Boldin, A Chaudhry, LL Lin, KD Taganov, T Hanada, A Yoshimura, D Baltimore…
Cell, 2010cell.com
Summary 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 …
Summary
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.
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