TGF-β and retinoic acid induce miR-10a, which targets Bcl-6 and constrains helper T cell plasticity

Distinct CD4 + T cell subsets are critical for host defense and immunoregulation. While these subsets can behave as terminally differentiated lineages, elements of plasticity are increasingly recognized. MicroRNAs are one factor that controls stability and plasticity. Herein, we report that miR-10a...

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Veröffentlicht in:Nature immunology 2012-04, Vol.13 (6), p.587-595
Hauptverfasser: Takahashi, Hayato, Kanno, Tomohiko, Nakayamada, Shingo, Hirahara, Kiyoshi, Sciumè, Giuseppe, Muljo, Stefan A., Kuchen, Stefan, Casellas, Rafael, Wei, Lai, Kanno, Yuka, O'Shea, John J.
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Sprache:eng
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Zusammenfassung:Distinct CD4 + T cell subsets are critical for host defense and immunoregulation. While these subsets can behave as terminally differentiated lineages, elements of plasticity are increasingly recognized. MicroRNAs are one factor that controls stability and plasticity. Herein, we report that miR-10a was highly expressed in naturally-occurring regulatory T (T reg ) cells and induced by retinoic acid and TGF-β in inducible T reg cells. By simultaneously targeting Bcl-6 and a co-repressor, Ncor2, miR-10a attenuated phenotypic conversion of inducible T reg cells to follicular helper T cells. miR-10a also limited T H 17 differentiation and therefore represents a new factor that can fine tune plasticity and fate decision of helper T cells.
ISSN:1529-2908
1529-2916
DOI:10.1038/ni.2286