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Its importance goes beyond its abstract link with human autoimmune disease. <jats:italic>Aire<\/jats:italic> identification opened new perspectives to better understand the molecular basis of central tolerance and self\u2013non\u2010self distinction, the main properties of the immune system. Since 1997, a growing number of immunologists and molecular geneticists have made important discoveries about the function of <jats:italic>Aire<\/jats:italic>, which is essentially a pleiotropic gene. <jats:italic>Aire<\/jats:italic> is one of the functional markers in medullary thymic epithelial cells (m<jats:styled-content style=\"fixed-case\">TEC<\/jats:styled-content>s), controlling their differentiation and expression of peripheral tissue antigens (<jats:styled-content style=\"fixed-case\">PTA<\/jats:styled-content>s), m<jats:styled-content style=\"fixed-case\">TEC<\/jats:styled-content>\u2013thymocyte adhesion and the expression of micro<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>s, among other functions. With <jats:italic>Aire<\/jats:italic>, the immunological tolerance became even more apparent from the molecular genetics point of view. Currently, m<jats:styled-content style=\"fixed-case\">TEC<\/jats:styled-content>s represent the most unusual cells because they express almost the entire functional genome but still maintain their identity. Due to the enormous diversity of <jats:styled-content style=\"fixed-case\">PTA<\/jats:styled-content>s, this uncommon gene expression pattern was termed promiscuous gene expression, the interpretation of which is essentially immunological \u2013 i.e. it is related to self\u2010representation in the thymus. Therefore, this knowledge is strongly linked to the negative selection of autoreactive thymocytes. In this update, we focus on the most relevant results of <jats:italic>Aire<\/jats:italic> as a transcriptional and post\u2010transcriptional controller of <jats:styled-content style=\"fixed-case\">PTA<\/jats:styled-content>s in m<jats:styled-content style=\"fixed-case\">TEC<\/jats:styled-content>s, its mechanism of action, and its influence on the negative selection of autoreactive thymocytes as the bases of the induction of central tolerance and prevention of autoimmune diseases.<\/jats:p>","DOI":"10.1111\/imm.12831","type":"journal-article","created":{"date-parts":[[2017,9,5]],"date-time":"2017-09-05T02:08:48Z","timestamp":1504577328000},"page":"10-20","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":81,"title":["Update on <i>Aire<\/i> and thymic negative selection"],"prefix":"10.1111","volume":"153","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4408-140X","authenticated-orcid":false,"given":"Geraldo 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