HIF-2α-dependent induction of miR-29a restrains TH1 activity during T cell dependent colitis.
Nat Commun
; 15(1): 8042, 2024 Sep 14.
Article
em En
| MEDLINE
| ID: mdl-39271652
ABSTRACT
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 TH1-driven colitis. In this work, we show a previously unrecognized function for hypoxia-dependent induction of miR-29a in attenuating TH1-mediated inflammation.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Colite
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Células Th1
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MicroRNAs
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Fatores de Transcrição Hélice-Alça-Hélice Básicos
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article