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While many of the components and mechanisms of maternal\u2010fetal tolerance have been investigated in detail and previously and thoroughly reviewed (Erlebacher A. <jats:italic>Annu Rev Immunol<\/jats:italic>. 2013;<jats:bold>31<\/jats:bold>:387\u2013411), the role of autoimmune regulator (<jats:italic>Aire<\/jats:italic>), a critical regulator of central tolerance expressed by medullary thymic epithelial cells (mTECs), has been less explored. Aire is known to facilitate the expression of a range of otherwise tissue\u2010specific antigens (TSAs) in mTECs, and here we highlight recent work showing a role for mTEC\u2010mediated thymic selection in maintaining maternal\u2010fetal tolerance. Recently, however, our group and others have identified additional populations of extrathymic Aire\u2010expressing cells (eTACs) in the secondary lymphoid organs. These hematopoietic antigen\u2010presenting cells possess the ability to induce functional inactivation and\/or deletion of cognate T cells, and deletion of maternal eTACs during pregnancy increases T\u2010cell activation in the lymph nodes and lymphocytic infiltration of the uterus, leading to pregnancy complications including intrauterine growth restriction (IUGR) and fetal resorption. In this review, we briefly summarize findings related to essential Aire biology, discuss the known roles of Aire\u2010deficiency related to pregnancy complications and infertility, review the newly discovered role for eTACs in the maintenance of maternal\u2010fetal tolerance\u2014as well as recent work defining eTACs at the single\u2010cell level\u2014and postulate potential mechanisms by which eTACs may regulate this process.<\/jats:p>","DOI":"10.1111\/imr.13082","type":"journal-article","created":{"date-parts":[[2022,5,10]],"date-time":"2022-05-10T07:21:05Z","timestamp":1652167265000},"page":"93-104","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Thymic and extrathymic <i>Aire<\/i>\u2010expressing cells in maternal\u2010fetal tolerance*"],"prefix":"10.1111","volume":"308","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0288-2062","authenticated-orcid":false,"given":"Im\u2010Hong","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Surgery University of California  San Francisco California USA"},{"name":"Diabetes Center University of California  San Francisco California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5071-9572","authenticated-orcid":false,"given":"Eva","family":"Gillis\u2010Buck","sequence":"additional","affiliation":[{"name":"Department of Surgery University of California  San Francisco California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5232-809X","authenticated-orcid":false,"given":"Tippi C.","family":"Mackenzie","sequence":"additional","affiliation":[{"name":"Department of Surgery University of California  San Francisco California USA"},{"name":"Center for 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