{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T22:51:29Z","timestamp":1785883889155,"version":"3.56.0"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,1,12]],"date-time":"2023-01-12T00:00:00Z","timestamp":1673481600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>The \u03b3\u03b4T cells that produce IL-17 (\u03b3\u03b4T17 cells) play a key role in various pathophysiologic processes in host defense and homeostasis. The development of \u03b3\u03b4T cells in the thymus requires \u03b3\u03b4T cell receptor (\u03b3\u03b4TCR) signaling mediated by the spleen tyrosine kinase (Syk) family proteins, Syk and Zap70. Here, we show a critical role of Syk in the early phase of \u03b3\u03b4T cell development using mice deficient for Syk specifically in lymphoid lineage cells (Syk-conditional knockout (cKO) mice). The development of \u03b3\u03b4T cells in the Syk-cKO mice was arrested at the precursor stage where the expression of Rag genes and \u03b1\u03b2T-lineage-associated genes were retained, indicating that Syk is required for \u03b3\u03b4T-cell lineage commitment. Loss of Syk in \u03b3\u03b4T cells weakened TCR signal-induced phosphorylation of Erk and Akt, which is mandatory for the thymic development of \u03b3\u03b4T17 cells. Syk-cKO mice exhibited a loss of \u03b3\u03b4T17 cells in the thymus as well as throughout the body, and thereby are protected from \u03b3\u03b4T17-dependent psoriasis-like skin inflammation. Collectively, our results indicate that Syk is a key player in the lineage commitment of \u03b3\u03b4T cells and the priming of \u03b3\u03b4T17 cell differentiation. <\/jats:p>","DOI":"10.3389\/fimmu.2022.1045881","type":"journal-article","created":{"date-parts":[[2023,1,12]],"date-time":"2023-01-12T05:56:16Z","timestamp":1673502976000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Spleen tyrosine kinase mediates the \u03b3\u03b4TCR signaling required for \u03b3\u03b4T cell commitment and \u03b3\u03b4T17 differentiation"],"prefix":"10.3389","volume":"13","author":[{"given":"Ryunosuke","family":"Muro","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoya","family":"Narita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Nitta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Takayanagi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,1,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-022-00746-9","article-title":"IL-17 and IL-17-producing cells in protection versus pathology","volume":"5","author":"Mills","year":"2022","journal-title":"Nat Rev 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