Negative Regulation of Hif1a Expression and T(H)17 Differentiation by Hypoxia Regulated miR-210

MicroRNA-210 (miR-210) is a signature microRNA of hypoxia. We found robust increase (>100-fold) of miR-210 abundance in activated T cells, especially in the T(H)17 lineage. Hypoxia synergized with T cell receptor (TCR)–CD28 stimulation to accelerate and increase the magnitude of Mir210 expression. Mir210 was directly regulated by HIF-1α, a key regulator of T(H)17 polarization. Surprisingly, Hif1a was identified as a miR-210-target, suggesting negative-feedback by miR-210 to inhibit HIF-1α protein expression. Deletion of Mir210 promoted T(H)17 differentiation under conditions with limited oxygen. In experimental colitis, miR-210 reduced Hif1a transcript abundance, reduced the proportion of cells producing 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.