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

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• 作者：Li-Fan Lu ; Mark P. Boldin ; Ashutosh Chaudhry ; Ling-Li Lin ; Konstantin D. Taganov ; Toshikatsu Hanada ; Akihiko Yoshimura ; David Baltimore ; Alex ; er Y. Rudensky
• 刊名：Cell
• 出版年：2010
• 出版时间：17 September 2010
• 年：2010
• 卷：142
• 期：6
• 页码：914-929
• 全文大小：2580 K

文摘

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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