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

PLoS One. 2011;6(5):e20171. doi: 10.1371/journal.pone.0020171. Epub 2011 May 26.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Cell Differentiation / genetics
  • Cell Polarity / genetics
  • Cells, Cultured
  • Gene Expression Regulation*
  • Genetic Loci
  • Humans
  • Interleukin-17 / biosynthesis*
  • Interleukin-17 / genetics*
  • Interleukin-23 / metabolism
  • Mice
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Molecular Sequence Data
  • Receptors, Antigen, T-Cell, alpha-beta / metabolism*
  • Receptors, Antigen, T-Cell, gamma-delta / metabolism*
  • Synteny / genetics
  • Th17 Cells / cytology
  • Th17 Cells / metabolism*


  • Interleukin-17
  • Interleukin-23
  • MIRN133 microRNA, human
  • MIRN206 microRNA, human
  • MicroRNAs
  • Mirn133 microRNA, mouse
  • Mirn206 microRNA, mouse
  • Receptors, Antigen, T-Cell, alpha-beta
  • Receptors, Antigen, T-Cell, gamma-delta