{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Cheng MI"],"funding":["DOD | USA | MEDCOM | MRDC | U.S. Army Medical Research Acquisition Activity","NCATS NIH HHS","HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases","NIDDK NIH HHS","NIAID NIH HHS","HHS | NIH | National Institute of Neurological Disorders and Stroke","HHS | NIH | National Institute of Allergy and Infectious Diseases","NINDS NIH HHS","NIGMS NIH HHS"],"pagination":["1069-1074"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10948288"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["212(7)"],"pubmed_abstract":["Hypoxia is a hallmark of inflammatory conditions (e.g., inflammatory bowel disease [IBD]), and adaptive responses have consequently evolved to protect against hypoxia-associated tissue injury. Because augmenting hypoxia-induced protective responses is a promising therapeutic approach for IBD, a more complete understanding of these pathways is needed. Recent work has demonstrated that the histone demethylase UTX is oxygen-sensitive, but its role in IBD is unclear. In this study, we show that hypoxia-induced deactivation of UTX downregulates T cell responses in mucosal inflammation. Hypoxia results in decreased T cell proinflammatory cytokine production and increased immunosuppressive regulatory T cells, and these findings are recapitulated by UTX deficiency. Hypoxia leads to T cell accumulation of H3K27me3 histone modifications, suggesting that hypoxia impairs UTX's histone demethylase activity to dampen T cell colitogenic activity. Finally, T cell-specific UTX deletion ameliorates colonic inflammation in an IBD mouse model, implicating UTX's oxygen-sensitive demethylase activity in counteracting hypoxic inflammation."],"journal":["Journal of immunology (Baltimore, Md. : 1950)"],"pubmed_title":["Cutting Edge: Hypoxia Sensing by the Histone Demethylase UTX (KDM6A) Limits Colitogenic CD4+ T Cells in Mucosal Inflammation."],"pmcid":["PMC10948288"],"funding_grant_id":["R01 AI174519","R01 DK119445","R01 AI143894","T32 GM007185","PR200530","T32 AI007323","NS107851","AI143894","DK119445","K12 TR004410","R01 NS107851"],"pubmed_authors":["Hong L","Bustillos C","Sheikh SZ","Chin S","Vo A","Su MA","Chen B","Cheng MI","Luthers CR"],"additional_accession":[]},"is_claimable":false,"name":"Cutting Edge: Hypoxia Sensing by the Histone Demethylase UTX (KDM6A) Limits Colitogenic CD4+ T Cells in Mucosal Inflammation.","description":"Hypoxia is a hallmark of inflammatory conditions (e.g., inflammatory bowel disease [IBD]), and adaptive responses have consequently evolved to protect against hypoxia-associated tissue injury. Because augmenting hypoxia-induced protective responses is a promising therapeutic approach for IBD, a more complete understanding of these pathways is needed. Recent work has demonstrated that the histone demethylase UTX is oxygen-sensitive, but its role in IBD is unclear. In this study, we show that hypoxia-induced deactivation of UTX downregulates T cell responses in mucosal inflammation. Hypoxia results in decreased T cell proinflammatory cytokine production and increased immunosuppressive regulatory T cells, and these findings are recapitulated by UTX deficiency. Hypoxia leads to T cell accumulation of H3K27me3 histone modifications, suggesting that hypoxia impairs UTX's histone demethylase activity to dampen T cell colitogenic activity. Finally, T cell-specific UTX deletion ameliorates colonic inflammation in an IBD mouse model, implicating UTX's oxygen-sensitive demethylase activity in counteracting hypoxic inflammation.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Apr","modification":"2026-06-01T07:44:45.753Z","creation":"2025-07-04T03:05:48.677Z"},"accession":"S-EPMC10948288","cross_references":{"pubmed":["38353647"],"doi":["10.4049/jimmunol.2300550"]}}