Haas, JD;
Nistala, K;
Petermann, F;
Saran, N;
Chennupati, V;
Schmitz, S;
Korn, T;
... Prinz, I; + view all
(2011)
Expression of miRNAs miR-133b and miR-206 in the Il17a/f Locus Is Co-Regulated with IL-17 Production in alpha beta and gamma delta T Cells.
PLOS ONE
, 6
(5)
, Article e20171. 10.1371/journal.pone.0020171.
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Abstract
Differentiation of T helper 17 cells (Th17) is a multistep process that involves the cytokines IL-6, TGF-beta, and IL-23 as well as IL-1 beta, IL-21, and TNF-alpha. 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 gamma delta 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 alpha beta and gamma delta 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.
| Type: | Article |
|---|---|
| Title: | Expression of miRNAs miR-133b and miR-206 in the Il17a/f Locus Is Co-Regulated with IL-17 Production in alpha beta and gamma delta T Cells |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1371/journal.pone.0020171 |
| Publisher version: | http://dx.doi.org/10.1371/journal.pone.0020171 |
| Language: | English |
| Additional information: | © 2011 Haas et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. This work was supported by the German Research Foundation (DFG, www.dfg.de; Emmy-Noether Program, KR2320/2-1 and EXC62, “Rebirth,” A.K.; and SFB621-A14, I.P.). Open Access Publication supported by the DFG. JH, VC and NS are scholars of the Hannover Biomedical Research School. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. |
| Keywords: | SKELETAL-MUSCLE, LINEAGE DIFFERENTIATION, TH17 CELLS, MICRORNAS, CYTOKINE, COFUNCTIONALITY, INTERLEUKIN-17, INFLAMMATION, REGENERATION, COEXPRESSION |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1311317 |
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