{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T23:35:45Z","timestamp":1787009745684,"version":"build-2736575974"},"reference-count":47,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2013,7,23]],"date-time":"2013-07-23T00:00:00Z","timestamp":1374537600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2013,10]]},"abstract":"<jats:p>\n                    Thymic\u2010derived CD4\n                    <jats:sup>+<\/jats:sup>\n                    CD25\n                    <jats:sup>+<\/jats:sup>\n                    Foxp3\n                    <jats:sup>+<\/jats:sup>\n                    natural regulatory T (nT\n                    <jats:sub>reg<\/jats:sub>\n                    ) cells are essential for the maintenance of peripheral immune tolerance. Signaling pathways that drive immature thymic progenitors to differentiate into CD4\n                    <jats:sup>+<\/jats:sup>\n                    CD25\n                    <jats:sup>+<\/jats:sup>\n                    Foxp3\n                    <jats:sup>+<\/jats:sup>\n                    nT\n                    <jats:sub>reg<\/jats:sub>\n                    cells need to be elucidated. The precise role of the TSC1\/2 complex, a critical negative regulator of mammalian target of rapamycin (mTOR), in thymic CD4\n                    <jats:sup>+<\/jats:sup>\n                    CD25\n                    <jats:sup>+<\/jats:sup>\n                    Foxp3\n                    <jats:sup>+<\/jats:sup>\n                    nT\n                    <jats:sub>reg<\/jats:sub>\n                    \u2010cell develop ment remains elusive. In the present study, we found that the percentage and cell number of thymic CD4\n                    <jats:sup>+<\/jats:sup>\n                    CD25\n                    <jats:sup>+<\/jats:sup>\n                    Foxp3\n                    <jats:sup>+<\/jats:sup>\n                    nT\n                    <jats:sub>reg<\/jats:sub>\n                    cells were significantly increased in T\u2010cell\u2010specific TSC1\u2010knockout (TSC1KO) mice. Nevertheless, the levels of CD4\n                    <jats:sup>+<\/jats:sup>\n                    CD25\n                    <jats:sup>+<\/jats:sup>\n                    Foxp3\n                    <jats:sup>\u2013<\/jats:sup>\n                    nT\n                    <jats:sub>reg<\/jats:sub>\n                    precursors in TSC1KO thymus were indistinguishable from those in wild\u2010type mice. TSC1KO CD4\n                    <jats:sup>+<\/jats:sup>\n                    CD25\n                    <jats:sup>+<\/jats:sup>\n                    Foxp3\n                    <jats:sup>+<\/jats:sup>\n                    nT\n                    <jats:sub>reg<\/jats:sub>\n                    cells showed normal cell death but enhanced proliferative response to IL\u20102 in a STAT5\u2010dependent manner. Rapamycin (Rapa) treatment failed to rescue but rather increased the frequency of CD4\n                    <jats:sup>+<\/jats:sup>\n                    CD25\n                    <jats:sup>+<\/jats:sup>\n                    Foxp3\n                    <jats:sup>+<\/jats:sup>\n                    nT\n                    <jats:sub>reg<\/jats:sub>\n                    cells in TSC1KO and RictorKO mice. The percentage and cell number of thymic CD4\n                    <jats:sup>+<\/jats:sup>\n                    CD25\n                    <jats:sup>+<\/jats:sup>\n                    Foxp3\n                    <jats:sup>+<\/jats:sup>\n                    nT\n                    <jats:sub>reg<\/jats:sub>\n                    cells were significantly increased in T\u2010cell\u2010specific RictorKO mice but not in PtenKO mice. Collectively, our studies suggest that TSC1 plays an important role in regulating thymic CD4\n                    <jats:sup>+<\/jats:sup>\n                    CD25\n                    <jats:sup>+<\/jats:sup>\n                    Foxp3\n                    <jats:sup>+<\/jats:sup>\n                    nT\n                    <jats:sub>reg<\/jats:sub>\n                    \u2010cell development\n                    <jats:italic>via<\/jats:italic>\n                    a Rapa\u2010resistant and mTORC2\u2010dependent signaling pathway.\u2014Chen, H, Zhang, L., Zhang, H., Xiao, Y., Shao, L., Li, H., Yin, H., Wang, R., Liu, G., Corley, D., Yang, Z., Zhao, Y., Disruption of TSC1\/2 signaling complex reveals a checkpoint governing thymic CD4+CD25+Foxp3+ regulatory T\u2010cell development in mice. FASEB J. 27, 3979\u20133990 (2013).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.13-235408","type":"journal-article","created":{"date-parts":[[2013,7,24]],"date-time":"2013-07-24T13:11:26Z","timestamp":1374671486000},"page":"3979-3990","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Disruption of TSC1\/2 signaling complex reveals a checkpoint governing thymic CD4\n                    <sup>+<\/sup>\n                    CD25\n                    <sup>+<\/sup>\n                    Foxp3\n                    <sup>+<\/sup>\n                    regulatory T\u2010cell development in mice"],"prefix":"10.1096","volume":"27","author":[{"given":"Hui","family":"Chen","sequence":"first","affiliation":[{"name":"State Key Laboratory of Biomembrane and Membrane Biotechnology Institute of Zoology Chinese Academy of Sciences Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lianjun","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Biomembrane and Membrane Biotechnology Institute of Zoology Chinese Academy of Sciences Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongbing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pathophysiology National Laboratory of Medical Molecular Biology Institute of Basic Medical Sciences and School of Basic Medicine Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Xiao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Biomembrane and Membrane Biotechnology Institute of Zoology Chinese Academy of Sciences Beijing 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