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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,5,5]]},"abstract":"<jats:p>Th17 cell function is highly context-dependent and can be categorized into pathogenic and nonpathogenic Th17 cell subsets. Understanding the molecule control of pathogenic Th17 (pTh17) cell immunity will benefit the treatment for related autoimmune diseases. Here, we revealed that cytochrome P450 1B1 (CYP1B1) is highly upregulated during mice and human colitis. CYP1B1 promoted both colon inflammatory diseases and colitis-associated colorectal cancer via pTh17-dependent but microbiota-independent manner. Notably, CYP1B1 specifically dictated the differentiation and pathogenicity of pTh17 cells, while having no effects on nonpathogenic Th17 cell generation. Mechanistically, CYP1B1 deficiency disrupted intracellular redox homeostasis via decreased glutathione synthetase, leading to increased ROS and mitochondrial dysfunction of pTh17 cells. ROS elimination by N-acetylcysteine or ectopic glutathione synthetase expression restored mitochondrial fitness and promoted pTh17 cell survival and generation. Taken together, our findings uncover a T cell intrinsic CYP1B1\u2013ROS\u2013mitochondrial axis in driving pTh17 cell generation, interfering with this hub may be beneficial for pTh17 cell-related immunopathology.<\/jats:p>","DOI":"10.1073\/pnas.2527753123","type":"journal-article","created":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T17:37:36Z","timestamp":1777484256000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":0,"title":["Cytochrome P450 1B1 directs pathogenic Th17 cell generation and autoimmune disease by fine-tuning redox homeostasis and mitochondrial integrity"],"prefix":"10.1073","volume":"123","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-7516-3047","authenticated-orcid":false,"given":"Wenhao","family":"Hu","sequence":"first","affiliation":[{"name":"Department of Urology, State Key Laboratory of Virology and Biosafety, Medical Research Institute, Zhongnan Hospital of Wuhan University, Wuhan 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Hu Cytochrome P450 1B1 directs pathogenic Th17 cell generation and autoimmune disease by fine-tuning redox homeostasis and mitochondrial integrity. Gene Expression Omnibus. https:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE302396. 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