HIF-2α-dependent induction of miR-29a restrains T H 1 activity during T cell dependent colitis.

Autor: Czopik AK; Department of Anesthesiology, Critical Care and Pain Medicine, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA. Agnieszka.K.Czopik@uth.tmc.edu., McNamee EN; Mucosal Inflammation Program, University of Colorado Anschutz School of Medicine, Aurora, CO, USA.; Digestive Health Institute, Children's Hospital Colorado, Aurora, CO, USA., Vaughn V; Department of Anesthesiology, Critical Care and Pain Medicine, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA., Huang X; Department of Anesthesiology, Critical Care and Pain Medicine, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA., Bang IH; Department of Anesthesiology, Critical Care and Pain Medicine, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA., Clark T; Department of Anesthesiology, Critical Care and Pain Medicine, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA., Wang Y; Department of Anesthesiology, Critical Care and Pain Medicine, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA., Ruan W; Department of Anesthesiology, Critical Care and Pain Medicine, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA., Nguyen T; Mucosal Inflammation Program, University of Colorado Anschutz School of Medicine, Aurora, CO, USA.; Digestive Health Institute, Children's Hospital Colorado, Aurora, CO, USA., Masterson JC; Mucosal Inflammation Program, University of Colorado Anschutz School of Medicine, Aurora, CO, USA.; Gastrointestinal Eosinophilic Disease Program University of Colorado Anschutz School of Medicine, Aurora, CO, USA.; Department of Pediatrics, University of Colorado Anschutz School of Medicine, Aurora, CO, USA., Tak E; Digestive Health Institute, Children's Hospital Colorado, Aurora, CO, USA.; Department of Convergence Medicine, Asan Medical Institute of Convergence Science and Technology (AMIST), Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea., Frank S; Organ Protection Program, Department of Anesthesiology, University of Colorado - Anschutz Medical Campus, Aurora, CO, USA.; Department of Anaesthesiology, LMU University Hospital, LMU Munich, Munich, Germany., Collins CB; Mucosal Inflammation Program, University of Colorado Anschutz School of Medicine, Aurora, CO, USA.; Department of Pediatrics, University of Colorado Anschutz School of Medicine, Aurora, CO, USA., Li H; Division of Pulmonary Sciences and Critical Care Medicine, School of Medicine, University of Colorado - Anschutz Medical Campus, Aurora, CO, USA., Rodriguez-Aguayo C; Departmental of Experimental Therapeutics and Center for RNA Interference and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Lopez-Berestein G; Departmental of Experimental Therapeutics and Center for RNA Interference and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Gerich ME; Mucosal Inflammation Program, University of Colorado Anschutz School of Medicine, Aurora, CO, USA.; Division of Gastroenterology & Hepatology, University of Colorado Anschutz School of Medicine, Aurora, CO, USA., Furuta GT; Mucosal Inflammation Program, University of Colorado Anschutz School of Medicine, Aurora, CO, USA.; Gastrointestinal Eosinophilic Disease Program University of Colorado Anschutz School of Medicine, Aurora, CO, USA.; Department of Pediatrics, University of Colorado Anschutz School of Medicine, Aurora, CO, USA., Yuan X; Department of Anesthesiology, Critical Care and Pain Medicine, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA., Sood AK; Departmental of Experimental Therapeutics and Center for RNA Interference and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.; Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., de Zoeten EF; Mucosal Inflammation Program, University of Colorado Anschutz School of Medicine, Aurora, CO, USA. Edwin.DeZoeten@childrenscolorado.org.; Department of Pediatrics, University of Colorado Anschutz School of Medicine, Aurora, CO, USA. Edwin.DeZoeten@childrenscolorado.org., Eltzschig HK; Department of Anesthesiology, Critical Care and Pain Medicine, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA.; Center for Outcomes Research, Department of Anesthesiology, Critical Care and Pain Medicine, McGovern Medical School, The University of Texas Health Science Center, Houston, TX, USA.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Sep 14; Vol. 15 (1), pp. 8042. Date of Electronic Publication: 2024 Sep 14.
DOI: 10.1038/s41467-024-52113-y
Abstrakt: 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 T H 1-driven colitis. In this work, we show a previously unrecognized function for hypoxia-dependent induction of miR-29a in attenuating T H 1-mediated inflammation.
(© 2024. The Author(s).)
Databáze: MEDLINE
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