{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T13:02:56Z","timestamp":1791291776340,"version":"4.1.0"},"reference-count":23,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2014,3,1]],"date-time":"2014-03-01T00:00:00Z","timestamp":1393632000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,3,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Understanding the cellular dynamics of Aire-expressing lineage(s) among medullary thymic epithelial cells (AEL-mTECs) is essential for gaining insight into the roles of Aire in establishment of self-tolerance. In this study, we monitored the maturation program of AEL-mTECs by temporal lineage tracing, in which bacterial artificial chromosome transgenic mice expressing tamoxifen-inducible Cre recombinase under control of the Aire regulatory element were crossed with reporter strains. We estimated that the half-life of AEL-mTECs subsequent to Aire expression was \u223c7\u20138 d, which was much longer than that reported previously, owing to the existence of a post-Aire stage. We found that loss of Aire did not alter the overall lifespan of AEL-mTECs, inconsistent with the previous notion that Aire expression in medullary thymic epithelial cells (mTECs) might result in their apoptosis for efficient cross-presentation of self-antigens expressed by AEL-mTECs. In contrast, Aire was required for the full maturation program of AEL-mTECs, as exemplified by the lack of physiological downregulation of CD80 during the post-Aire stage in Aire-deficient mice, thus accounting for the abnormally increased CD80high mTECs seen in such mice. Of interest, increased CD80high mTECs in Aire-deficient mice were not mTEC autonomous and were dependent on cross-talk with thymocytes. These results further support the roles of Aire in the differentiation program of AEL-mTECs.<\/jats:p>","DOI":"10.4049\/jimmunol.1302786","type":"journal-article","created":{"date-parts":[[2014,2,11]],"date-time":"2014-02-11T05:11:54Z","timestamp":1392095514000},"page":"2585-2592","source":"Crossref","is-referenced-by-count":68,"title":["Temporal Lineage Tracing of Aire-Expressing Cells Reveals a Requirement for Aire in Their Maturation Program"],"prefix":"10.1093","volume":"192","author":[{"given":"Yumiko","family":"Nishikawa","sequence":"first","affiliation":[{"name":"Division of Molecular Immunology, Institute for Enzyme Research, University of Tokushima , Tokushima 770-8503,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hitoshi","family":"Nishijima","sequence":"additional","affiliation":[{"name":"Division of Molecular Immunology, Institute for Enzyme Research, University of Tokushima , Tokushima 770-8503,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minoru","family":"Matsumoto","sequence":"additional","affiliation":[{"name":"Division of Molecular Immunology, Institute for Enzyme Research, University of Tokushima , Tokushima 770-8503,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junko","family":"Morimoto","sequence":"additional","affiliation":[{"name":"Division of Molecular Immunology, Institute for Enzyme Research, University of Tokushima , Tokushima 770-8503,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fumiko","family":"Hirota","sequence":"additional","affiliation":[{"name":"Division of Molecular Immunology, Institute for Enzyme Research, University of Tokushima , Tokushima 770-8503,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoru","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Institute of Basic Medical Sciences and Laboratory Animal Resource Center, Center for Tsukuba Advanced Research Alliance, University of Tsukuba , Tsukuba 305-8575,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herv\u00e9","family":"Luche","sequence":"additional","affiliation":[{"name":"Institute of Immunology, University Clinics Ulm , 89081 Ulm,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans Joerg","family":"Fehling","sequence":"additional","affiliation":[{"name":"Institute of Immunology, University Clinics Ulm , 89081 Ulm,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhiro","family":"Mouri","sequence":"additional","affiliation":[{"name":"Division of Molecular Immunology, Institute for Enzyme Research, University of Tokushima , Tokushima 770-8503,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsuru","family":"Matsumoto","sequence":"additional","affiliation":[{"name":"Division of Molecular Immunology, Institute for Enzyme Research, University of Tokushima , Tokushima 770-8503,","place":["Japan"]},{"name":"Japan Science and Technology Agency, Core Research for Evolutional Science and Technology , 102-8666 Tokyo,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2014,3,15]]},"reference":[{"key":"2025032404193177600_r1","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1146\/annurev.immunol.25.022106.141532","article-title":"Aire","volume":"27","author":"Mathis","year":"2009","journal-title":"Annu. 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