Abstract
Distinct CD4+ T cell subsets are critical for host defense and immunoregulation. Although these subsets can act as terminally differentiated lineages, they have been increasingly noted to demonstrated plasticity. MicroRNAs are factors that control T cell stability and plasticity. Here we report that naturally occurring regulatory T cells (Treg cells) had high expression of the microRNA miR-10a and that miR-10a was induced by retinoic acid and transforming growth factor-β (TGF-β) in inducible Treg cells. By simultaneously targeting the transcriptional repressor Bcl-6 and the corepressor Ncor2, miR-10a attenuated the phenotypic conversion of inducible Treg cells into follicular helper T cells. We also found that miR-10a limited differentiation into the TH17 subset of helper T cells and therefore represents a factor that can fine-tune the plasticity and fate of helper T cells.
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Acknowledgements
We thank Y. Belkaid, W. Chen and A. Villarino for reading this manuscript; K. Moro and T. Tamachi for advice on manipulating Peyer's patches; L. Naldini (San Raffaele Institute) for the LV-SFFV lentiviral vector; and J. Simone and J. Lay for cell sorting. Supported by the Japan Society for the Promotion of Science (Research Fellowship for Japanese Biomedical and Behavioral Researchers at the US National Institutes of Health to H.T. and K.H.), the Instituto Pasteur-Fondazione Cenci-Bolognetti (G.S.) and the Intramural Research Program of the National Institute of Arthritis, Musculoskeletal and Skin Diseases.
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H.T. designed, did, analyzed and interpreted all the experiments and wrote the manuscript; T.K., S.N., K.H., G.S., S.K. and L.W. helped with experiments; Y.K. contributed to data interpretation, helped with experiments and wrote the manuscript; S.A.M. and R.C. contributed to experimental design and provided suggestions; and J.J.O. contributed to experimental design, analyzed and interpreted all acquired data and wrote the manuscript.
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Takahashi, H., Kanno, T., Nakayamada, S. et al. TGF-β and retinoic acid induce the microRNA miR-10a, which targets Bcl-6 and constrains the plasticity of helper T cells. Nat Immunol 13, 587–595 (2012). https://doi.org/10.1038/ni.2286
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DOI: https://doi.org/10.1038/ni.2286
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