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
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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. / Haas, Jan D; Nistala, Kiran; Petermann, Franziska; Saran, Namita; Chennupati, Vijaykumar; Schmitz, Susanne; Korn, Thomas; Wedderburn, Lucy R; Förster, Reinhold; Krueger, Andreas; Prinz, Immo.
In: PLOS ONE, Vol. 6, No. 5, 2011, p. e20171.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - 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
AU - Haas, Jan D
AU - Nistala, Kiran
AU - Petermann, Franziska
AU - Saran, Namita
AU - Chennupati, Vijaykumar
AU - Schmitz, Susanne
AU - Korn, Thomas
AU - Wedderburn, Lucy R
AU - Förster, Reinhold
AU - Krueger, Andreas
AU - Prinz, Immo
PY - 2011
Y1 - 2011
N2 - 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.
AB - 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.
KW - Animals
KW - Base Sequence
KW - Cell Differentiation/genetics
KW - Cell Polarity/genetics
KW - Cells, Cultured
KW - Gene Expression Regulation
KW - Genetic Loci
KW - Humans
KW - Interleukin-17/biosynthesis
KW - Interleukin-23/metabolism
KW - Mice
KW - MicroRNAs/genetics
KW - Molecular Sequence Data
KW - Receptors, Antigen, T-Cell, alpha-beta/metabolism
KW - Receptors, Antigen, T-Cell, gamma-delta/metabolism
KW - Synteny/genetics
KW - Th17 Cells/cytology
U2 - 10.1371/journal.pone.0020171
DO - 10.1371/journal.pone.0020171
M3 - SCORING: Journal article
C2 - 21637854
VL - 6
SP - e20171
JO - PLOS ONE
JF - PLOS ONE
SN - 1932-6203
IS - 5
ER -