Negative regulation of Hif1a expression and TH17 differentiation by the hypoxia-regulated microRNA miR-210

Nat Immunol. 2014 Apr;15(4):393-401. doi: 10.1038/ni.2846. Epub 2014 Mar 9.


The microRNA miR-210 is a signature of hypoxia. We found robust increase in the abundance of miR-210 (>100-fold) in activated T cells, especially in the TH17 lineage of helper T cells. Hypoxia acted in synergy with stimulation via the T cell antigen receptor (TCR) and coreceptor CD28 to accelerate and increase Mir210 expression. Mir210 was directly regulated by HIF-1α, a key transcriptional regulator of TH17 polarization. Unexpectedly, we identified Hif1a as a target of miR-210, which suggested negative feedback by miR-210 in inhibiting HIF-1α expression. Deletion of Mir210 promoted TH17 differentiation under conditions of limited oxygen. In experimental colitis, miR-210 reduced the abundance of Hif1a transcripts and the proportion of cells that produced inflammatory cytokines and controlled disease severity. Our study identifies miR-210 as an important regulator of T cell differentiation in hypoxia, which can limit immunopathology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4 Antigens / metabolism
  • Cell Differentiation / genetics
  • Cell Hypoxia / immunology
  • Cells, Cultured
  • Colitis, Ulcerative / immunology*
  • Cytokines / metabolism
  • Disease Models, Animal
  • Disease Progression
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
  • Lymphocyte Activation / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • RNA Interference / immunology
  • T-Lymphocyte Subsets / cytology
  • T-Lymphocyte Subsets / immunology*
  • Th17 Cells / cytology
  • Th17 Cells / immunology*


  • CD4 Antigens
  • Cytokines
  • Hif1a protein, mouse
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • MIRN210 microRNA, mouse
  • MicroRNAs