{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T13:51:02Z","timestamp":1789480262916,"version":"build-2803163510"},"reference-count":90,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"39","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2024,9,27]]},"abstract":"<jats:p>\n            Central tolerance of thymocytes to self-antigen depends on the medullary thymic epithelial cell (mTEC) transcription factor autoimmune regulator (Aire), which drives tissue-restricted antigen (TRA) gene expression. Vitamin D signaling regulates Aire and TRA expression in mTECs, providing a basis for links between vitamin D deficiency and autoimmunity. We find that mice lacking Cyp27b1, which cannot produce hormonally active vitamin D, display profoundly reduced thymic cellularity, with a reduced proportion of Aire\n            <jats:sup>+<\/jats:sup>\n            mTECs, attenuated TRA expression, and poorly defined cortical-medullary boundaries. Markers of T cell negative selection are diminished, and organ-specific autoantibodies are present in knockout (KO) mice. Single-cell RNA sequencing revealed that loss of Cyp27b1 skews mTEC differentiation toward Ccl21\n            <jats:sup>+<\/jats:sup>\n            intertypical TECs and generates a gene expression profile consistent with premature aging. KO thymi display accelerated involution and reduced expression of thymic longevity factors. Thus, loss of thymic vitamin D signaling disrupts normal mTEC differentiation and function and accelerates thymic aging.\n          <\/jats:p>","DOI":"10.1126\/sciadv.adm9582","type":"journal-article","created":{"date-parts":[[2024,9,25]],"date-time":"2024-09-25T19:00:24Z","timestamp":1727290824000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":12,"title":["Skewed epithelial cell differentiation and premature aging of the thymus in the absence of vitamin D signaling"],"prefix":"10.1126","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-8671-333X","authenticated-orcid":true,"given":"Patricio","family":"Artusa","sequence":"first","affiliation":[{"name":"Department of Physiology, McGill University, Montreal QC, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-7505-2481","authenticated-orcid":true,"given":"Loan","family":"Nguyen Yamamoto","sequence":"additional","affiliation":[{"name":"Department of Medicine, McGill University, Montreal QC, Canada."},{"name":"Calcium Research Laboratory, McGill University Health Centre, Montreal QC, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camille","family":"Barbier","sequence":"additional","affiliation":[{"name":"Department of Physiology, McGill University, Montreal QC, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie F.","family":"Valbon","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Infectious Disease, Universit\u00e9 de Montr\u00e9al, Montreal, QC, Canada."},{"name":"Rosalind and Morris Goodman Cancer Institute, McGill University, Montreal, QC, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-4087-3041","authenticated-orcid":true,"given":"Yashar","family":"Aghazadeh Habashi","sequence":"additional","affiliation":[{"name":"Department of Physiology, McGill University, Montreal QC, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0222-4182","authenticated-orcid":true,"given":"Haig","family":"Djambazian","sequence":"additional","affiliation":[{"name":"McGill University Genome Centre, McGill University, Montreal, QC, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5530-5336","authenticated-orcid":true,"given":"Aiten","family":"Ismailova","sequence":"additional","affiliation":[{"name":"Department of Physiology, McGill University, Montreal QC, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8087-4810","authenticated-orcid":true,"given":"Marie-\u00c8ve","family":"Lebel","sequence":"additional","affiliation":[{"name":"Maisonneuve-Rosemont Hospital Research Center, McGill University, Montreal, QC, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reyhaneh","family":"Salehi-Tabar","sequence":"additional","affiliation":[{"name":"Department of Physiology, McGill University, Montreal QC, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-4144-943X","authenticated-orcid":true,"given":"Fatemeh","family":"Sarmadi","sequence":"additional","affiliation":[{"name":"Department of Physiology, McGill University, Montreal QC, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8515-0934","authenticated-orcid":true,"given":"Jiannis","family":"Ragoussis","sequence":"additional","affiliation":[{"name":"McGill University Genome Centre, McGill University, Montreal, QC, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Goltzman","sequence":"additional","affiliation":[{"name":"Department of Medicine, McGill University, Montreal QC, Canada."},{"name":"Calcium Research Laboratory, McGill University Health Centre, Montreal QC, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0951-334X","authenticated-orcid":true,"given":"Heather J.","family":"Melichar","sequence":"additional","affiliation":[{"name":"Rosalind and Morris Goodman Cancer Institute, McGill University, Montreal, QC, Canada."},{"name":"Department of Microbiology and Immunology, McGill University, Montreal, QC, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4785-2687","authenticated-orcid":true,"given":"John H.","family":"White","sequence":"additional","affiliation":[{"name":"Department of Physiology, McGill University, Montreal QC, Canada."},{"name":"Department of Medicine, McGill University, Montreal QC, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri3667"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-019-0238-0"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/acel.13671"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2018.04.010"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0346-1"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1700203"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0345-2"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.imlet.2019.01.012"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1500558"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni1160"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80195-8"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2013.08.038"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200737131"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20070795"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20080866"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1217532110"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.25.022106.141532"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3327"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.3884"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.2300207"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1210\/er.2018-00126"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.4065\/mcp.2010.0567"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1515\/jpem-2012-0021"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40618-016-0432-x"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1177\/153537020422901108"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.3390\/nu12051233"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.131029498"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0711558105"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1002545"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.18.9831"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2011.05.045"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.766698"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1900191"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-13456-z"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20121458"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/11.4.397"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.174.4.1862"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1075958"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0073862"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2016.5531"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1038\/373531a0"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.172.4.2067"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.176.7.3995"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1105677"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni982"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2007.07.017"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.60188"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2014.08.070"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2019101828"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-21346-6"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2022.05.018"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201545677"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0414-6"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-020-0591-3"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2015.00365"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1913776117"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1514511113"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-04-149435"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.18632\/aging.101903"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-04752-8"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.21.24.8592-8604.2001"},{"key":"e_1_3_2_63_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.133.4.1748"},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(01)06580-1"},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1440-1711.2003.01191.x"},{"key":"e_1_3_2_66_2","doi-asserted-by":"publisher","DOI":"10.5603\/GP.2016.0008"},{"key":"e_1_3_2_67_2","doi-asserted-by":"publisher","DOI":"10.30699\/jogcr.7.6.536"},{"key":"e_1_3_2_68_2","doi-asserted-by":"publisher","DOI":"10.1210\/er.2008-0004"},{"key":"e_1_3_2_69_2","doi-asserted-by":"publisher","DOI":"10.1038\/bonekey.2014.5"},{"key":"e_1_3_2_70_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2006-2664"},{"key":"e_1_3_2_71_2","doi-asserted-by":"publisher","DOI":"10.1210\/endo.142.12.8650"},{"key":"e_1_3_2_72_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.15.7861"},{"key":"e_1_3_2_73_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-004-1329-3"},{"key":"e_1_3_2_74_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0003-9861(03)00338-2"},{"key":"e_1_3_2_75_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0003-9861(02)00580-5"},{"key":"e_1_3_2_76_2","doi-asserted-by":"publisher","DOI":"10.2337\/db07-1095"},{"key":"e_1_3_2_77_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12016-013-8361-3"},{"key":"e_1_3_2_78_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI111557"},{"key":"e_1_3_2_79_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2172-15-6"},{"key":"e_1_3_2_80_2","first-page":"12","article-title":"1\u03b1,25(OH)2D3 inhibits not only Th1 but also Th2 differentiation in human cord blood T cells","volume":"52","author":"Pichler J.","year":"2002","unstructured":"J. Pichler, M. Gerstmayr, Z. Szepfalusi, R. Urbanek, M. Peterlik, M. Willheim, 1\u03b1,25(OH)2D3 inhibits not only Th1 but also Th2 differentiation in human cord blood T cells. Pediatr. Res. 52, 12\u201318 (2002).","journal-title":"Pediatr. Res."},{"key":"e_1_3_2_81_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.163790"},{"key":"e_1_3_2_82_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jnutbio.2013.09.003"},{"key":"e_1_3_2_83_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.10580"},{"key":"e_1_3_2_84_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.168.3.1181"},{"key":"e_1_3_2_85_2","doi-asserted-by":"publisher","DOI":"10.5115\/acb.2011.44.1.14"},{"key":"e_1_3_2_86_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.56221"},{"key":"e_1_3_2_87_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12979-020-0173-8"},{"key":"e_1_3_2_88_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1474-9726.2007.00365.x"},{"key":"e_1_3_2_89_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-37511-9"},{"key":"e_1_3_2_90_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12902-024-01541-4"},{"key":"e_1_3_2_91_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2019.05.045"}],"container-title":["Science Advances"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/sciadv.adm9582","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,25]],"date-time":"2024-09-25T19:01:18Z","timestamp":1727290878000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/sciadv.adm9582"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,27]]},"references-count":90,"journal-issue":{"issue":"39","published-print":{"date-parts":[[2024,9,27]]}},"alternative-id":["10.1126\/sciadv.adm9582"],"URL":"https:\/\/doi.org\/10.1126\/sciadv.adm9582","relation":{},"ISSN":["2375-2548"],"issn-type":[{"value":"2375-2548","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,27]]},"assertion":[{"value":"2023-11-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-08-19","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-09-25","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eadm9582"}}