{"doi":"10.7554/elife.89270","title":"Vitamin D constrains inflammation by modulating the expression of key genes on Chr17q12-21.1","abstract":"Vitamin D possesses immunomodulatory functions and vitamin D deficiency has been associated with the rise in chronic inflammatory diseases, including asthma (Litonjua and Weiss, 2007). Vitamin D supplementation studies do not provide insight into the molecular genetic mechanisms of vitamin D-mediated immunoregulation. Here, we provide evidence for vitamin D regulation of two human chromosomal loci, Chr17q12-21.1 and Chr17q21.2, reliably associated with autoimmune and chronic inflammatory diseases. We demonstrate increased vitamin D receptor ( Vdr ) expression in mouse lung CD4+ Th2 cells, differential expression of Chr17q12-21.1 and Chr17q21.2 genes in Th2 cells based on vitamin D status and identify the IL-2/Stat5 pathway as a target of vitamin D signaling. Vitamin D deficiency caused severe lung inflammation after allergen challenge in mice that was prevented by long-term prenatal vitamin D supplementation. Mechanistically, vitamin D induced the expression of the Ikzf3 -encoded protein Aiolos to suppress IL-2 signaling and ameliorate cytokine production in Th2 cells. These translational findings demonstrate mechanisms for the immune protective effect of vitamin D in allergic lung inflammation with a strong molecular genetic link to the regulation of both Chr17q12-21.1 and Chr17q21.2 genes and suggest further functional studies and interventional strategies for long-term prevention of asthma and other autoimmune disorders.","journal":"eLife","year":2023,"id":346592,"datarank":0.5368059702460688,"base_score":2.5649493574615367,"endowment":2.5649493574615367,"self_citation_contribution":0.38474240361923057,"citation_network_contribution":0.15206356662683818,"self_endowment_contribution":0.38474240361923057,"citer_contribution":0.15206356662683818,"corpus_percentile":null,"corpus_rank":null,"citation_count":12,"citer_count":11,"citers_with_citation_signal":5,"citers_with_endowment":5,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9469,"is_data_producer":true,"deposit_databanks":{"GEO":["GSE89431","GSE22484"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":559214,"name":"Arda Halu","orcid":"0000-0001-6217-790X","position":1,"is_corresponding":false},{"id":320640,"name":"Margherita De Marzio","orcid":"0000-0003-1821-208X","position":2,"is_corresponding":false},{"id":506800,"name":"Enrico Maiorino","orcid":"0000-0002-0159-4221","position":3,"is_corresponding":false},{"id":706673,"name":"Melody G. 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Brüggemann","orcid":"0000-0003-3961-618X","position":5,"is_corresponding":false},{"id":1087994,"name":"Joselyn J Rojas Quintero","orcid":null,"position":6,"is_corresponding":false},{"id":461862,"name":"Robert Chase","orcid":"0000-0003-1183-0619","position":7,"is_corresponding":false},{"id":252195,"name":"Hooman Mirzakhani","orcid":"0000-0002-2290-4436","position":8,"is_corresponding":false},{"id":1087434,"name":"Ayse Özge Sungur","orcid":"0000-0002-9272-9717","position":9,"is_corresponding":false},{"id":1087995,"name":"Janine Koepke","orcid":null,"position":10,"is_corresponding":false},{"id":274957,"name":"Taiji Nakano","orcid":"0000-0001-7499-1204","position":11,"is_corresponding":false},{"id":1077002,"name":"Hong Yong Peh","orcid":"0000-0001-6098-9381","position":12,"is_corresponding":false},{"id":687795,"name":"Nandini Krishnamoorthy","orcid":"0000-0002-1114-7118","position":13,"is_corresponding":false},{"id":4667,"name":"Raja-Elie E. Abdulnour","orcid":"0000-0002-8053-0145","position":14,"is_corresponding":false},{"id":492590,"name":"Katia Georgopoulos","orcid":"0000-0002-8963-4258","position":15,"is_corresponding":false},{"id":252193,"name":"Augusto A. Litonjua","orcid":"0000-0003-0422-5875","position":16,"is_corresponding":false},{"id":368597,"name":"Marie B. Demay","orcid":"0000-0001-5845-5479","position":17,"is_corresponding":false},{"id":559519,"name":"Harald Renz","orcid":"0000-0003-0602-7215","position":18,"is_corresponding":false},{"id":40860,"name":"Bruce D. Levy","orcid":"0000-0001-9515-5731","position":19,"is_corresponding":false},{"id":25033,"name":"Scott T. 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