{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T00:16:49Z","timestamp":1792455409532,"version":"4.5.0"},"reference-count":75,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2023,4,1]],"date-time":"2023-04-01T00:00:00Z","timestamp":1680307200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100002570","name":"American Association of Immunologists","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100002570","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The thymus is an intricate organ consisting of a diverse population of thymic epithelial cells (TECs). Cortical and medullary TECs and their subpopulations have distinct roles in coordinating the development and selection of functionally competent and self-tolerant T cells. Recent advances made in technologies such as single-cell RNA sequencing have made it possible to investigate and resolve the heterogeneity in TECs. These findings have provided further understanding of the molecular mechanisms regulating TEC function and expression of tissue-restricted Ags. In this brief review, we focus on the newly characterized subsets of TECs and their diversity in relation to their functions in supporting T cell development. We also discuss recent discoveries in expression of self-antigens in the context of TEC development as well as the cellular and molecular changes occurring during embryonic development to thymic involution.<\/jats:p>","DOI":"10.4049\/jimmunol.2200610","type":"journal-article","created":{"date-parts":[[2023,3,22]],"date-time":"2023-03-22T21:09:00Z","timestamp":1679519340000},"page":"888-894","source":"Crossref","is-referenced-by-count":7,"title":["Investigating Thymic Epithelial Cell Diversity Using Systems Biology"],"prefix":"10.1093","volume":"210","author":[{"given":"Honyin","family":"Chiu","sequence":"first","affiliation":[{"name":"Benaroya Research Institute , Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8960-4307","authenticated-orcid":false,"given":"Peter S","family":"Linsley","sequence":"additional","affiliation":[{"name":"Benaroya Research Institute , Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven F","family":"Ziegler","sequence":"additional","affiliation":[{"name":"Benaroya Research Institute , Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,4,1]]},"reference":[{"key":"2025021008020649000_r1","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1146\/annurev-immunol-051116-052320","article-title":"Thymic epithelial cells","volume":"35","author":"Abramson","year":"2017","journal-title":"Annu. 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Immunol."},{"key":"2025021008020649000_r52","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1016\/j.coi.2009.05.009","article-title":"Effects of aging on T cell function","volume":"21","author":"Haynes","year":"2009","journal-title":"Curr. Opin. Immunol."},{"key":"2025021008020649000_r53","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1016\/j.smim.2012.04.009","article-title":"Age-related changes in CD8 T cell homeostasis and immunity to infection","volume":"24","author":"Nikolich-\u017dugich","year":"2012","journal-title":"Semin. Immunol."},{"key":"2025021008020649000_r54","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1002\/eji.201142305","article-title":"Molecular control over thymic involution: from cytokines and microRNA to aging and adipose tissue","volume":"42","author":"Dooley","year":"2012","journal-title":"Eur. J. Immunol."},{"key":"2025021008020649000_r55","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1016\/j.it.2009.04.003","article-title":"Thymic involution and immune reconstitution","volume":"30","author":"Lynch","year":"2009","journal-title":"Trends Immunol."},{"key":"2025021008020649000_r56","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1016\/j.coi.2013.06.002","article-title":"Thymic rejuvenation and aging","volume":"25","author":"Ventevogel","year":"2013","journal-title":"Curr. Opin. Immunol."},{"key":"2025021008020649000_r57","doi-asserted-by":"crossref","first-page":"316","DOI":"10.3389\/fimmu.2013.00316","article-title":"The effect of age on thymic function","volume":"4","author":"Palmer","year":"2013","journal-title":"Front. 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Biol."},{"key":"2025021008020649000_r68","doi-asserted-by":"crossref","first-page":"5693","DOI":"10.4049\/jimmunol.179.9.5693","article-title":"Lymphotoxin pathway and Aire influences on thymic medullary epithelial cells are unconnected","volume":"179","author":"Venanzi","year":"2007","journal-title":"J. Immunol."},{"key":"2025021008020649000_r69","doi-asserted-by":"crossref","first-page":"1976","DOI":"10.4049\/jimmunol.165.4.1976","article-title":"Normal thymic architecture and negative selection are associated with Aire expression, the gene defective in the autoimmune-polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED)","volume":"165","author":"Zuklys","year":"2000","journal-title":"J. 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