title: Expression of miRNAs miR-133b and miR-206 in the Il17a/f locus is co-regulated with IL-17 production in αβ and γδ T cells.
abstract: Differentiation of T helper 17 cells (Th17) is a multistep process that involves the cytokines IL-6, TGF-β, and IL-23 as well as IL-1β, IL-21, and TNF-α. Thereby, robust induction of the capacity to produce IL-17 involves epigenetic modifications of the syntenic Il17a/f locus. Using inbred mouse strains, we identified co-regulation of gene transcription at the Il17a/f locus with the nearby microRNAs miR-133b and miR-206 that are clustered approximately 45 kb upstream of Il17a/f. Expression of these microRNAs was specific for Th17 as compared to other CD4(+) T cell subsets and this was equally valid for in vitro polarized and ex vivo derived cells. From all factors analyzed, IL-23 was the most important cytokine for the in vitro induction of miR-133b and miR-206 in naive CD4(+) T cells of wild type mice. However, analysis of IL-23R deficient mice revealed that IL-23R signaling was not essential for the induction of miR-133b and miR-206. Importantly, we found a similar co-regulation in CCR6(+) and other γδ T cell subsets that are predisposed to production of IL-17. Taken together, we discovered a novel feature of T cell differentiation towards an IL-17-producing phenotype that is shared between αβ and γδ T cells. Notably, the specific co-regulation of miR-133b and miR-206 with the Il17a/f locus also extended to human Th17 cells. This qualifies expression of miR-133b and miR-206 in T cells as novel biomarkers for Th17-type immune reactions.
authors.affiliation: Institute for Immunology, Hannover Medical School, Hannover, Germany.
authors.forename: Jan D
authors.initials: JD
authors.lastname: Haas
authors.forename: Kiran
authors.initials: K
authors.lastname: Nistala
authors.forename: Franziska
authors.initials: F
authors.lastname: Petermann
authors.forename: Namita
authors.initials: N
authors.lastname: Saran
authors.forename: Vijaykumar
authors.initials: V
authors.lastname: Chennupati
authors.forename: Susanne
authors.initials: S
authors.lastname: Schmitz
authors.forename: Thomas
authors.initials: T
authors.lastname: Korn
authors.forename: Lucy R
authors.initials: LR
authors.lastname: Wedderburn
authors.forename: Reinhold
authors.initials: R
authors.lastname: Förster
authors.forename: Andreas
authors.initials: A
authors.lastname: Krueger
authors.forename: Immo
authors.initials: I
authors.lastname: Prinz
mesh_terms: D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation / Q000235:genetics; D016764:Cell Polarity / Q000235:genetics; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D056426:Genetic Loci; D006801:Humans; D020381:Interleukin-17 / Q000096:biosynthesis* / Q000235:genetics*; D053759:Interleukin-23 / Q000378:metabolism; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism*; D026801:Synteny / Q000235:genetics; D058504:Th17 Cells / Q000166:cytology / Q000378:metabolism*
chemical_list: D020381:Interleukin-17; D053759:Interleukin-23; C548234:MIRN133 microRNA, human; C546087:MIRN206 microRNA, human; D035683:MicroRNAs; C517732:Mirn133 microRNA, mouse; C540669:Mirn206 microRNA, mouse; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta