{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T12:35:52Z","timestamp":1792067752935,"version":"4.4.0"},"reference-count":224,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,5,13]],"date-time":"2021-05-13T00:00:00Z","timestamp":1620864000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["GM137493"],"award-info":[{"award-number":["GM137493"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>The mechanistic target of rapamycin (mTOR) controls cell fate and responses via its functions in regulating metabolism. Its role in controlling immunity was unraveled by early studies on the immunosuppressive properties of rapamycin. Recent studies have provided insights on how metabolic reprogramming and mTOR signaling impact peripheral T cell activation and fate. The contribution of mTOR and metabolism during early T-cell development in the thymus is also emerging and is the subject of this review. Two major T lineages with distinct immune functions and peripheral homing organs diverge during early thymic development; the \u03b1\u03b2- and \u03b3\u03b4-T cells, which are defined by their respective TCR subunits. Thymic T-regulatory cells, which have immunosuppressive functions, also develop in the thymus from positively selected \u03b1\u03b2-T cells. Here, we review recent findings on how the two mTOR protein complexes, mTORC1 and mTORC2, and the signaling molecules involved in the mTOR pathway are involved in thymocyte differentiation. We discuss emerging views on how metabolic remodeling impacts early T cell development and how this can be mediated via mTOR signaling.<\/jats:p>","DOI":"10.3390\/genes12050728","type":"journal-article","created":{"date-parts":[[2021,5,13]],"date-time":"2021-05-13T11:10:06Z","timestamp":1620904206000},"page":"728","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["MTOR Signaling and Metabolism in Early T Cell Development"],"prefix":"10.3390","volume":"12","author":[{"given":"Guy","family":"Werlen","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Robert Wood Johnson Medical School, Rutgers University, Piscataway, NJ 08854, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ritika","family":"Jain","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Robert Wood Johnson Medical School, Rutgers University, Piscataway, NJ 08854, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7118-1759","authenticated-orcid":false,"given":"Estela","family":"Jacinto","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Robert Wood Johnson Medical School, Rutgers University, Piscataway, NJ 08854, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"a028621","DOI":"10.1101\/cshperspect.a028621","article-title":"Cytokines, Transcription Factors, and the Initiation of T-Cell Development","volume":"10","author":"Hosokawa","year":"2018","journal-title":"Cold Spring Harb. 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