{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:30:42Z","timestamp":1792801842519,"version":"4.5.0"},"reference-count":46,"publisher":"Rockefeller University Press","issue":"12","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2014,11,17]]},"abstract":"<jats:p>Medullary thymic epithelial cells (mTECs) expressing the autoimmune regulator AIRE and various tissue-specific antigens (TSAs) are critical for preventing the onset of autoimmunity and may attenuate tumor immunity. However, molecular mechanisms controlling mTEC development remain elusive. Here, we describe the roles of the transcription factor Spi-B in mTEC development. Spi-B is rapidly up-regulated by receptor activator of NF-\u03baB ligand (RANKL) cytokine signaling, which triggers mTEC differentiation, and in turn up-regulates CD80, CD86, some TSAs, and the natural inhibitor of RANKL signaling, osteoprotegerin (OPG). Spi-B\u2013mediated OPG expression limits mTEC development in neonates but not in embryos, suggesting developmental stage\u2013specific negative feedback regulation. OPG-mediated negative regulation attenuates cellularity of thymic regulatory T cells and tumor development in vivo. Hence, these data suggest that this negative RANKL\u2013Spi-B\u2013OPG feedback mechanism finely tunes mTEC development and function and may optimize the trade-off between prevention of autoimmunity and induction of antitumor immunity.<\/jats:p>","DOI":"10.1084\/jem.20141207","type":"journal-article","created":{"date-parts":[[2014,11,11]],"date-time":"2014-11-11T05:04:12Z","timestamp":1415682252000},"page":"2425-2438","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":73,"title":["Limitation of immune tolerance\u2013inducing thymic epithelial cell development by Spi-B\u2013mediated negative feedback regulation"],"prefix":"10.1084","volume":"211","author":[{"given":"Nobuko","family":"Akiyama","sequence":"first","affiliation":[{"name":"Division of Cellular and Molecular Biology, Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo 108-8639, Japan 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