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 (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(H)17 subset of helper T cells and therefore represents a factor that can fine-tune the plasticity and fate of helper T cells.
authors.affiliation: Molecular Immunology and Inflammation Branch, National Institute of Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Hayato
authors.initials: H
authors.lastname: Takahashi
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Kanno
authors.forename: Shingo
authors.initials: S
authors.lastname: Nakayamada
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Hirahara
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Sciumè
authors.forename: Stefan A
authors.initials: SA
authors.lastname: Muljo
authors.forename: Stefan
authors.initials: S
authors.lastname: Kuchen
authors.forename: Rafael
authors.initials: R
authors.lastname: Casellas
authors.forename: Lai
authors.initials: L
authors.lastname: Wei
authors.forename: Yuka
authors.initials: Y
authors.lastname: Kanno
authors.forename: John J
authors.initials: JJ
authors.lastname: O'Shea
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D015536:Down-Regulation / Q000276:immunology; D005434:Flow Cytometry; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D056985:Nuclear Receptor Co-Repressor 2 / Q000276:immunology; D010641:Phenotype; D051560:Proto-Oncogene Proteins c-bcl-6 / Q000276:immunology / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020825:T-Box Domain Proteins / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects* / Q000276:immunology / Q000502:physiology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology / Q000502:physiology; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014212:Tretinoin / Q000494:pharmacology*; D000098815:T-bet Transcription Factor
chemical_list: C569259:MIRN10 microRNA, mouse; D035683:MicroRNAs; C539131:Ncor2 protein, mouse; D056985:Nuclear Receptor Co-Repressor 2; D051560:Proto-Oncogene Proteins c-bcl-6; D012333:RNA, Messenger; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D016212:Transforming Growth Factor beta; D014212:Tretinoin