{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T01:21:04Z","timestamp":1775092864096,"version":"3.50.1"},"reference-count":52,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T00:00:00Z","timestamp":1756339200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001691","name":"KAKENHI","doi-asserted-by":"publisher","award":["20K07460"],"award-info":[{"award-number":["20K07460"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"KAKENHI","doi-asserted-by":"publisher","award":["23K06513"],"award-info":[{"award-number":["23K06513"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012319","name":"National Center for Global Health and Medicine","doi-asserted-by":"publisher","award":["(25-103)"],"award-info":[{"award-number":["(25-103)"]}],"id":[{"id":"10.13039\/100012319","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,2,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Themis (thymocyte-expressed molecule involved in selection) is a T-cell-specific protein that is critically required for positive selection in the thymus. However, its function in T-cell receptor (TCR) responses during allergic skin inflammation remains unclear. To investigate the function of Themis in peripheral T cells, we generated tamoxifen-induced Themis conditional knockout (cKO) mice. The deletion of Themis by tamoxifen treatment significantly reduced ear swelling and CD8 T-cell infiltration induced by hapten 2,4-dinitrofluorobenzene (DNFB) challenge, which activates CD8 T cells. The CD8 T cells in the inflamed skin from Themis cKO mice showed decreased interferon gamma (IFN\u03b3) production and T-bet and Eomes expression. Furthermore, the transgenic overexpression of Themis enhanced DNFB-induced allergic skin responses. However, Themis cKO mice showed unaltered skin inflammation induced by fluorescein isothiocyanate\/dibutyl phthalate, which activates CD4 T cells. The TCR-stimulated proliferation and IFN\u03b3 production of Themis cKO na\u00efve CD8 T cells were significantly decreased in vitro, whereas the proliferation and cytokine production of CD4 T cells were not altered. As expected, the administration of the SHP-1\/2 inhibitor restored the reduced IFN\u03b3 production in Themis cKO CD8 T cells in vitro. Mice harboring mutant Themis lacking the Grb2-binding site showed a similar phenotype to Themis cKO mice, indicating that the function of Themis in peripheral CD8 T cells is dependent on Grb2 binding. Collectively, these results suggest that Themis regulates the threshold of TCR signaling in peripheral CD8 T cells, but not in CD4 T cells.<\/jats:p>","DOI":"10.1093\/intimm\/dxaf050","type":"journal-article","created":{"date-parts":[[2025,8,27]],"date-time":"2025-08-27T11:45:42Z","timestamp":1756295142000},"page":"107-117","source":"Crossref","is-referenced-by-count":1,"title":["Role of Themis in peripheral CD8 T cells in hapten-induced allergic skin inflammation"],"prefix":"10.1093","volume":"38","author":[{"given":"Masayuki","family":"Kitajima","sequence":"first","affiliation":[{"name":"Department of Immunology and Pathology, Research Institute, National Center for Global Health and Medicine , Chiba, 272-8516 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshiyuki","family":"Okada","sequence":"additional","affiliation":[{"name":"Department of Immunology and Pathology, Research Institute, National Center for Global Health and Medicine , Chiba, 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