Function of miR-146a in controlling Treg cell-mediated regulation of Th1 responses Journal Article
| Authors: | Lu, L. F. ; Boldin, M. P.; Chaudhry, A.; Lin, L. L.; Taganov, K. D.; Hanada, T.; Yoshimura, A.; Baltimore, D.; Rudensky, A. Y. |
| Article Title: | Function of miR-146a in controlling Treg cell-mediated regulation of Th1 responses |
| 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 IFN gamma-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 IFN gamma 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. |
| Keywords: | transcription factor foxp3; cytokine; target genes; differentiation; signaling pathways; ifn-gamma; immune-responses; cd4(+); t-reg-cells; socs1 |
| Journal Title: | Cell |
| Volume: | 142 |
| Issue: | 6 |
| ISSN: | 0092-8674 |
| Publisher: | Cell Press |
| Date Published: | 2010-09-17 |
| Start Page: | 914 |
| End Page: | 929 |
| Language: | English |
| ACCESSION: | ISI:000281855000014 |
| DOI: | 10.1016/j.cell.2010.08.012 |
| PROVIDER: | wos |
| PMCID: | PMC3049116 |
| PUBMED: | 20850013 |
| Notes: | --- - Article - "Source: Wos" |
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