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
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 str...
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Published in | PloS one Vol. 6; no. 5; p. e20171 |
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Main Authors | , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Public Library of Science
2011
Public Library of Science (PLoS) |
Subjects | |
Online Access | Get full text |
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Summary: | 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. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Conceived and designed the experiments: JDH IP AK TK LRW RF. Performed the experiments: JDH KN FP NS VC SS AK IP. Analyzed the data: JDH KN FP NS VC SS AK IP. Contributed reagents/materials/analysis tools: KN LRW FP TK. Wrote the paper: JDH AK IP. |
ISSN: | 1932-6203 1932-6203 |
DOI: | 10.1371/journal.pone.0020171 |