{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T20:05:50Z","timestamp":1789243550716,"version":"build-2803163510"},"reference-count":28,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2027,2,1]],"date-time":"2027-02-01T00:00:00Z","timestamp":1801440000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2027,2,1]],"date-time":"2027-02-01T00:00:00Z","timestamp":1801440000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T00:00:00Z","timestamp":1788566400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","award":["financial code 001"],"award-info":[{"award-number":["financial code 001"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2017\/10780-4"],"award-info":[{"award-number":["2017\/10780-4"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2021\/0245-9"],"award-info":[{"award-number":["2021\/0245-9"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["302060\/2019-7"],"award-info":[{"award-number":["302060\/2019-7"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["441682\/2023-5"],"award-info":[{"award-number":["441682\/2023-5"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["311304\/2021-4"],"award-info":[{"award-number":["311304\/2021-4"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Immunology Letters"],"published-print":{"date-parts":[[2027,2]]},"DOI":"10.1016\/j.imlet.2026.107238","type":"journal-article","created":{"date-parts":[[2026,9,6]],"date-time":"2026-09-06T14:47:27Z","timestamp":1788706047000},"page":"107238","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"special_numbering":"C","title":["Aire deficiency disrupts thymic architecture but preserves TCRV\u03b2 repertoire diversity while altering thymic output"],"prefix":"10.1016","volume":"283","author":[{"given":"Adriana Arruda","family":"Matos","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7973-512X","authenticated-orcid":false,"given":"Itau\u00e1 Leston","family":"Araujo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matheus Dominato","family":"Munuera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patr\u00edcia Viana Bonini","family":"Palma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camila","family":"Bonaldo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Let\u00edcia Agrelli","family":"Brito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniella Ar\u00eaas","family":"Mendes-da-Cruz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilson","family":"Savino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4408-140X","authenticated-orcid":false,"given":"Geraldo Aleixo","family":"Passos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo Ant\u00f4nio","family":"Donadi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.imlet.2026.107238_bib0001","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1007\/978-3-031-77921-3_6","article-title":"Thymic crosstalk: an overview of the complex cellular interactions that control the establishment of T-cell tolerance","volume":"1471","author":"Irla","year":"2025","journal-title":"Adv. Exp. Med. Biol."},{"issue":"7","key":"10.1016\/j.imlet.2026.107238_bib0002","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1016\/j.it.2023.04.008","article-title":"Towards a quantitative theory of tolerance","volume":"44","author":"Mora","year":"2023","journal-title":"Trends Immunol."},{"issue":"10","key":"10.1016\/j.imlet.2026.107238_bib0003","doi-asserted-by":"crossref","DOI":"10.1084\/jem.20230896","article-title":"Adjusting to self in the thymus: CD4 versus CD8 lineage commitment and regulatory T cell development","volume":"221","author":"Baldwin","year":"2024","journal-title":"J. Exp. Med."},{"key":"10.1016\/j.imlet.2026.107238_bib0004","doi-asserted-by":"crossref","DOI":"10.1016\/j.imlet.2024.106861","article-title":"Thymocyte migration and emigration","volume":"267","author":"Tong","year":"2024","journal-title":"Immunol. Lett."},{"key":"10.1016\/j.imlet.2026.107238_bib0005","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1007\/978-3-031-77921-3_9","article-title":"The thymus as a mirror of the body's gene expression","volume":"1471","author":"Passos","year":"2025","journal-title":"Adv. Exp. Med. Biol."},{"key":"10.1016\/j.imlet.2026.107238_bib0006","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1007\/978-3-031-77921-3_5","article-title":"Intrathymic cell migration: implications in thymocyte development and T lymphocyte repertoire formation","volume":"1471","author":"Mendes-da-Cruz","year":"2025","journal-title":"Adv. Exp. Med. Biol."},{"key":"10.1016\/j.imlet.2026.107238_bib0007","doi-asserted-by":"crossref","first-page":"98","DOI":"10.3389\/fimmu.2018.00098","article-title":"Twenty Years of AIRE","volume":"9","author":"Perniola","year":"2018","journal-title":"Front. Immunol."},{"issue":"1\u20132","key":"10.1016\/j.imlet.2026.107238_bib0008","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.jim.2009.11.007","article-title":"A reliable and simplified sj\/beta-TREC ratio quantification method for human thymic output measurement","volume":"352","author":"Ferrando-Mart\u00ednez","year":"2010","journal-title":"J. Immunol. Methods"},{"key":"10.1016\/j.imlet.2026.107238_bib0009","doi-asserted-by":"crossref","first-page":"12","DOI":"10.3389\/fimmu.2011.00012","article-title":"PID comes full circle: applications of V(D)J recombination excision circles in research, diagnostics and newborn screening of primary immunodeficiency disorders","volume":"2","author":"van Zelm","year":"2011","journal-title":"Front. Immunol."},{"key":"10.1016\/j.imlet.2026.107238_bib0010","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.3389\/fimmu.2020.01341","article-title":"Evaluating thymic function after human hematopoietic stem cell transplantation in the personalized medicine era","volume":"11","author":"Gaballa","year":"2020","journal-title":"Front. Immunol."},{"key":"10.1016\/j.imlet.2026.107238_bib0011","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1007\/978-3-031-77921-3_10","article-title":"The CRISPR-Cas9 system is used to edit the autoimmune regulator gene in vitro and in vivo","volume":"1471","author":"Tanaka","year":"2025","journal-title":"Adv. Exp. Med. Biol."},{"issue":"11","key":"10.1016\/j.imlet.2026.107238_bib0012","doi-asserted-by":"crossref","first-page":"7818","DOI":"10.4049\/jimmunol.181.11.7818","article-title":"The magnitude of thymic output is genetically determined through controlled intrathymic precursor T cell proliferation","volume":"181","author":"Dulude","year":"2008","journal-title":"J. Immunol."},{"key":"10.1016\/j.imlet.2026.107238_bib0013","doi-asserted-by":"crossref","first-page":"481","DOI":"10.3389\/fimmu.2020.00481","article-title":"Assessment of thymic output dynamics after in utero infection of mice with coxsackievirus B4","volume":"11","author":"Halouani","year":"2020","journal-title":"Front. Immunol."},{"issue":"2","key":"10.1016\/j.imlet.2026.107238_bib0014","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1084\/jem.20091669","article-title":"Chronic mucocutaneous candidiasis in APECED or thymoma patients correlates with autoimmunity to Th17-associated cytokines","volume":"207","author":"Kisand","year":"2010","journal-title":"J. Exp. Med."},{"issue":"2","key":"10.1016\/j.imlet.2026.107238_bib0015","doi-asserted-by":"crossref","DOI":"10.1242\/dmm.046359","article-title":"AIRE deficiency, from preclinical models to human APECED disease","volume":"14","author":"Besnard","year":"2021","journal-title":"Dis. Model. Mech."},{"issue":"3","key":"10.1016\/j.imlet.2026.107238_bib0016","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1111\/j.1399-0039.2007.00992.x","article-title":"Genetic analysis of autoimmune regulator haplotypes in alopecia areata","volume":"71","author":"Wengraf","year":"2008","journal-title":"Tissue Antigens."},{"issue":"2","key":"10.1016\/j.imlet.2026.107238_bib0017","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.jaut.2006.06.001","article-title":"Aire deficient mice do not develop the same profile of tissue-specific autoantibodies as APECED patients","volume":"27","author":"P\u00f6ntynen","year":"2006","journal-title":"J. Autoimmun."},{"issue":"6","key":"10.1016\/j.imlet.2026.107238_bib0018","doi-asserted-by":"crossref","first-page":"3902","DOI":"10.4049\/jimmunol.0802124","article-title":"Aire-deficient C57BL\/6 mice mimicking the common human 13-base pair deletion mutation present with only a mild autoimmune phenotype","volume":"182","author":"Hubert","year":"2009","journal-title":"J. Immunol."},{"issue":"21","key":"10.1016\/j.imlet.2026.107238_bib0019","doi-asserted-by":"crossref","DOI":"10.1172\/JCI169704","article-title":"A partial form of AIRE deficiency underlies a mild form of autoimmune polyendocrine syndrome type 1","volume":"133","author":"Oftedal","year":"2023","journal-title":"J. Clin. Invest."},{"issue":"5597","key":"10.1016\/j.imlet.2026.107238_bib0020","doi-asserted-by":"crossref","first-page":"1395","DOI":"10.1126\/science.1075958","article-title":"Projection of an immunological self shadow within the thymus by the aire protein","volume":"298","author":"Anderson","year":"2002","journal-title":"Science"},{"issue":"1","key":"10.1016\/j.imlet.2026.107238_bib0021","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1186\/s12860-022-00414-9","article-title":"The absence of the autoimmune regulator gene (AIRE) impairs the three-dimensional structure of medullary thymic epithelial cell spheroids","volume":"23","author":"Monteleone-Cassiano","year":"2022","journal-title":"BMC. Mol. Cell Biol."},{"issue":"11","key":"10.1016\/j.imlet.2026.107238_bib0022","doi-asserted-by":"crossref","first-page":":841-8","DOI":"10.1016\/S0161-5890(01)00122-5","article-title":"T cell receptor excision circle assessment of thymopoiesis in aging mice","volume":"38","author":"Sempowski","year":"2002","journal-title":"Mol. Immunol."},{"issue":"1","key":"10.1016\/j.imlet.2026.107238_bib0023","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1038\/s41398-022-02159-7","article-title":"Blood levels of T-cell receptor excision circles (TRECs) provide an index of exposure to traumatic stress in mice and humans","volume":"12","author":"McCullough","year":"2022","journal-title":"Transl. Psychiatry"},{"issue":"4","key":"10.1016\/j.imlet.2026.107238_bib0024","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/j.jaut.2010.07.008","article-title":"Regulatory T cell defect in APECED patients is associated with loss of naive FOXP3(+) precursors and impaired activated population","volume":"35","author":"Laakso","year":"2010","journal-title":"J. Autoimmun."},{"issue":"9","key":"10.1016\/j.imlet.2026.107238_bib0025","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1016\/0167-5699(93)90249-K","article-title":"Is TCR beta expression an essential event in early thymocyte development?","volume":"14","author":"Palmer","year":"1993","journal-title":"Immunol. Today"},{"key":"10.1016\/j.imlet.2026.107238_bib0026","doi-asserted-by":"crossref","first-page":"1913","DOI":"10.1038\/s12276-025-01535-9","article-title":"Th17 cell pathogenicity in autoimmune disease","volume":"57","author":"Park","year":"2025","journal-title":"Exp. Mol. Med."},{"issue":"7","key":"10.1016\/j.imlet.2026.107238_bib0027","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1038\/ni.3194","article-title":"The deacetylase Sirt1 is an essential regulator of Aire-mediated induction of central immunological tolerance","volume":"16","author":"Chuprin","year":"2015","journal-title":"Nat. Immunol."},{"key":"10.1016\/j.imlet.2026.107238_bib0028","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2022.948419","article-title":"The AIRE G228W mutation disturbs the interaction of AIRE with its partner molecule SIRT1","volume":"13","author":"Santos","year":"2022","journal-title":"Front. Immunol."}],"container-title":["Immunology Letters"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0165247826001124?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0165247826001124?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T19:25:43Z","timestamp":1789241143000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0165247826001124"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2027,2]]},"references-count":28,"alternative-id":["S0165247826001124"],"URL":"https:\/\/doi.org\/10.1016\/j.imlet.2026.107238","relation":{},"ISSN":["0165-2478"],"issn-type":[{"value":"0165-2478","type":"print"}],"subject":[],"published":{"date-parts":[[2027,2]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Aire deficiency disrupts thymic architecture but preserves TCRV\u03b2 repertoire diversity while altering thymic output","name":"articletitle","label":"Article Title"},{"value":"Immunology Letters","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.imlet.2026.107238","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 The Author(s). Published by Elsevier B.V. on behalf of European Federation of Immunological Societies.","name":"copyright","label":"Copyright"}],"article-number":"107238"}}