{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:45:17Z","timestamp":1786977917887,"version":"build-2736575974"},"reference-count":43,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2020,12,2]],"date-time":"2020-12-02T00:00:00Z","timestamp":1606867200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Basic Research Program of China","doi-asserted-by":"publisher","award":["2017YFA0104402"],"award-info":[{"award-number":["2017YFA0104402"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Basic Research Program of China","doi-asserted-by":"publisher","award":["2017YFA0105002"],"award-info":[{"award-number":["2017YFA0105002"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2021,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The differentiation of mature medullary thymic epithelial cells (mTECs) is critical for the induction of central immune tolerance. Although the critical effect of mechanistic target of rapamycin complex 1 (mTORC1) in shaping mTEC differentiation has been studied, the regulatory role of mTORC2 in the differentiation and maturation of mTECs is poorly understood. We herein reported that TEC\u2010specific ablation of a rapamycin\u2010insensitive companion of mTOR (RICTOR), a key component of mTORC2, significantly decreased the thymus size and weight, the total cell number of TECs, and the cell number of mTECs with a smaller\u00a0degree of reduced cortical thymic epithelial cells. Interestingly, RICTOR deficiency significantly accelerated the mTEC maturation process, as indicated by the increased ratios of mature mTECs (MHCII\n                    <jats:sup>hi<\/jats:sup>\n                    , CD80\n                    <jats:sup>+<\/jats:sup>\n                    , and Aire\n                    <jats:sup>+<\/jats:sup>\n                    ) to immature mTECs (MHCII\n                    <jats:sup>lo<\/jats:sup>\n                    , CD80\n                    <jats:sup>\u2212<\/jats:sup>\n                    , and Aire\n                    <jats:sup>\u2212<\/jats:sup>\n                    ) in\n                    <jats:italic>Rictor<\/jats:italic>\n                    \u2010deficient mice. The RNA\u2010sequencing assays showed that the upregulated nuclear factor\u2010\u03baB\u00a0(NF\u2010\u03baB) signaling pathway in\n                    <jats:italic>Rictor<\/jats:italic>\n                    \u2010deficient mTECs was one of the obviously altered pathways compared with wild\u2010type mTECs. Our studies further showed that\n                    <jats:italic>Rictor<\/jats:italic>\n                    \u2010deficient mTECs exhibited upregulated expression of receptor activator of NF\u2010\u03baB (RANK) and lymphotoxin \u03b2 receptor (LT\u03b2R), as well as increased activity of canonical and noncanonical NF\u2010\u03baB signaling pathways as determined by ImageStream and Simple Western. Finally, our results showed that inhibition of NF\u2010\u03baB signaling pathways could partially reverse the accelerated maturation of mTECs in\n                    <jats:italic>Rictor<\/jats:italic>\n                    conditional KO mice. Thus, mTORC2 negatively controls the kinetics of the mTEC maturation process by inhibiting the LT\u03b2R\/RANK\u2010NF\u2010\u03baB signal axis.\n                  <\/jats:p>","DOI":"10.1002\/jcp.30192","type":"journal-article","created":{"date-parts":[[2020,12,2]],"date-time":"2020-12-02T23:35:40Z","timestamp":1606952140000},"page":"4725-4737","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["mTORC2 negatively controls the maturation process of medullary thymic epithelial cells by inhibiting the LT\u03b2R\/RANK\u2010NF\u2010\u03baB axis"],"prefix":"10.1002","volume":"236","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0410-2501","authenticated-orcid":false,"given":"Zhanfeng","family":"Liang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Membrane Biology, Institute of Zoology Chinese Academy of Sciences  Beijing China"},{"name":"University of Chinese Academy of Sciences  Beijing 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