Browse by Audience
Papers of the Week
HIF-2α-dependent induction of miR-29a restrains T1 activity during T cell dependent colitis.
Authors
Czopik AK, McNamee EN, Vaughn V, Huang X, Bang IH, Clark T, Wang Y, Ruan W, Nguyen T, Masterson JC, Tak E, Frank S, Collins CB, Li H, Rodriguez-Aguayo C, Lopez-Berestein G, Gerich ME, Furuta GT, Yuan X, Sood AK, de Zoeten EF, Eltzschig HKAbstract
Metabolic imbalance leading to inflammatory hypoxia and stabilization of hypoxia-inducible transcription factors (HIFs) is a hallmark of inflammatory bowel diseases. We hypothesize that HIF could be stabilized in CD4 T cells during intestinal inflammation and alter the functional responses of T cells via regulation of microRNAs. Our assays reveal markedly increased T cell-intrinsic hypoxia and stabilization of HIF protein during experimental colitis. microRNA screen in primary CD4 T cells points us towards miR-29a and our subsequent studies identify a selective role for HIF-2α in CD4-cell-intrinsic induction of miR-29a during hypoxia. Mice with T cell-intrinsic HIF-2α deletion display elevated T-bet (target of miR-29a) levels and exacerbated intestinal inflammation. Mice with miR-29a deficiency in T cells show enhanced intestinal inflammation. T cell-intrinsic overexpression of HIF-2α or delivery of miR-29a mimetic dampen T1-driven colitis. In this work, we show a previously unrecognized function for hypoxia-dependent induction of miR-29a in attenuating T1-mediated inflammation.
Come discuss this article and more at Pain Researcher!
