TGF-β and retinoic acid induce the microRNA miR-10a, which targets Bcl-6 and constrains the plasticity of helper T cells

Hayato Takahashi; Tomohiko Kanno; Shingo Nakayamada; Kiyoshi Hirahara; Giuseppe Sciumè; Stefan A. Muljo; Stefan Kuchen; Rafael Casellas; Lai Wei; Yuka Kanno; John J. O'Shea

doi:10.1038/ni.2286

TGF-β and retinoic acid induce the microRNA miR-10a, which targets Bcl-6 and constrains the plasticity of helper T cells

Hayato Takahashi, Tomohiko Kanno, Shingo Nakayamada, Kiyoshi Hirahara, Giuseppe Sciumè, Stefan A. Muljo, Stefan Kuchen, Rafael Casellas, Lai Wei, Yuka Kanno, John J. O'Shea

Research output: Contribution to journal › Article › peer-review

241 Citations (Scopus)

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 (T_reg 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 T _reg cells. By simultaneously targeting the transcriptional repressor Bcl-6 and the corepressor Ncor2, miR-10a attenuated the phenotypic conversion of inducible T_reg cells into follicular helper T cells. We also found that miR-10a limited differentiation into the T_H17 subset of helper T cells and therefore represents a factor that can fine-tune the plasticity and fate of helper T cells.

Original language	English
Pages (from-to)	587-595
Number of pages	9
Journal	Nature Immunology
Volume	13
Issue number	6
DOIs	https://doi.org/10.1038/ni.2286
Publication status	Published - 2012 Jun
Externally published	Yes

ASJC Scopus subject areas

Immunology and Allergy
Immunology

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title = "TGF-β and retinoic acid induce the microRNA miR-10a, which targets Bcl-6 and constrains the plasticity of helper T cells",

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 T reg 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.",

author = "Hayato Takahashi and Tomohiko Kanno and Shingo Nakayamada and Kiyoshi Hirahara and Giuseppe Scium{\`e} and Muljo, {Stefan A.} and Stefan Kuchen and Rafael Casellas and Lai Wei and Yuka Kanno and O'Shea, {John J.}",

note = "Funding Information: We thank Y. Belkaid, W. Chen and A. Villarino for reading this manuscript; K. Moro and T. Tamachi for advice on manipulating Peyer{\textquoteright}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.",

year = "2012",

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language = "English",

volume = "13",

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T1 - TGF-β and retinoic acid induce the microRNA miR-10a, which targets Bcl-6 and constrains the plasticity of helper T cells

AU - Takahashi, Hayato

AU - Kanno, Tomohiko

AU - Nakayamada, Shingo

AU - Hirahara, Kiyoshi

AU - Sciumè, Giuseppe

AU - Muljo, Stefan A.

AU - Kuchen, Stefan

AU - Casellas, Rafael

AU - Wei, Lai

AU - Kanno, Yuka

AU - O'Shea, John J.

N1 - Funding Information: 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.

PY - 2012/6

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N2 - 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 T reg 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.

AB - 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 T reg 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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TGF-β and retinoic acid induce the microRNA miR-10a, which targets Bcl-6 and constrains the plasticity of helper T cells

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