{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T18:14:35Z","timestamp":1783016075694,"version":"3.54.6"},"reference-count":54,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,5,14]],"date-time":"2021-05-14T00:00:00Z","timestamp":1620950400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["Intramural Research"],"award-info":[{"award-number":["Intramural Research"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Invariant NKT (<jats:italic>i<\/jats:italic>NKT) cells are thymus-generated innate-like T cells, comprised of three distinct subsets with divergent effector functions. The molecular mechanism that drives the lineage trifurcation of immature<jats:italic>i<\/jats:italic>NKT cells into the NKT1, NKT2, and NKT17 subsets remains a controversial issue that remains to be resolved. Because cytokine receptor signaling is necessary for<jats:italic>i<\/jats:italic>NKT cell generation, cytokines are proposed to contribute to<jats:italic>i<\/jats:italic>NKT subset differentiation also. However, the precise roles and requirements of cytokines in these processes are not fully understood. Here, we show that IL-2R\u03b2, a nonredundant component of the IL-15 receptor complex, plays a critical role in both the development and differentiation of thymic<jats:italic>i<\/jats:italic>NKT cells. While the induction of IL-2R\u03b2 expression on postselection thymocytes is necessary to drive the generation of<jats:italic>i<\/jats:italic>NKT cells, surprisingly, premature IL-2R\u03b2 expression on immature<jats:italic>i<\/jats:italic>NKT cells was detrimental to their development. Moreover, while IL-2R\u03b2 is necessary for NKT1 generation, paradoxically, we found that the increased abundance of IL-2R\u03b2 suppressed NKT1 generation without affecting NKT2 and NKT17 cell differentiation. Thus, the timing and abundance of IL-2R\u03b2 expression control<jats:italic>i<\/jats:italic>NKT lineage fate and development, thereby establishing cytokine receptor expression as a critical regulator of thymic<jats:italic>i<\/jats:italic>NKT cell differentiation.<\/jats:p>","DOI":"10.3389\/fimmu.2021.642856","type":"journal-article","created":{"date-parts":[[2021,5,14]],"date-time":"2021-05-14T09:04:28Z","timestamp":1620983068000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["The Timing and Abundance of IL-2R\u03b2 (CD122) Expression Control Thymic iNKT Cell Generation and NKT1 Subset Differentiation"],"prefix":"10.3389","volume":"12","author":[{"given":"Hee Yeun","family":"Won","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hye 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