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Intrathymic microenvironments are microanatomically compartmentalised, forming defined cortical, and medullary regions each differentially supporting critical aspects of thymus\u2010dependent T\u2010cell maturation. Importantly, the specific functional properties of thymic cortical and medullary compartments are defined by highly specialised thymic epithelial cells (TEC). For example, in the medulla heterogenous medullary TEC (mTEC) contribute to the enforcement of central tolerance by supporting deletion of autoreactive T\u2010cell clones, thereby counterbalancing the potential for random T\u2010cell receptor generation to contribute to autoimmune disease. Recent advances have further shed light on the pathways and mechanisms that control heterogeneous mTEC development and how differential mTEC functionality contributes to control self\u2010tolerant T\u2010cell development. Here we discuss recent findings in relation to mTEC development and highlight examples of how mTEC diversity contribute to thymus medulla function.<\/jats:p>","DOI":"10.1002\/bies.202300165","type":"journal-article","created":{"date-parts":[[2024,1,1]],"date-time":"2024-01-01T04:40:32Z","timestamp":1704084032000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Assembling the thymus medulla: Development and function of epithelial cell heterogeneity"],"prefix":"10.1002","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8811-6996","authenticated-orcid":false,"given":"Kieran D.","family":"James","sequence":"first","affiliation":[{"name":"Institute of Immunology and Immunotherapy University of Birmingham  Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilie J.","family":"Cosway","sequence":"additional","affiliation":[{"name":"Institute of Immunology and Immunotherapy 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