{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T15:20:09Z","timestamp":1787066409491,"version":"build-2736575974"},"reference-count":68,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2020,3,1]],"date-time":"2020-03-01T00:00:00Z","timestamp":1583020800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,3,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>During thymic development, mouse \u03b3\u03b4 T cells commit to either an IFN-\u03b3\u2013 or an IL-17\u2013producing phenotype through mechanisms that remain unclear. In this study, we investigated the extent to which the SLAM\/SAP signaling pathway regulates the functional programming of \u03b3\u03b4 T cells. Characterization of SLAM family receptor expression revealed that thymic \u03b3\u03b4 T cell subsets were each marked by distinct coexpression profiles of SLAMF1, SLAMF4, and SLAMF6. In the thymus, V\u03b31 and V\u03b34 T cells that exhibited an SLAMF1+SLAMF6+ double positive phenotype were largely contained within immature CD24+CD73\u2212 and CD24+CD73+ subsets, whereas SLAMF1 single positive, SLAMF6 single positive, or SLAMF1SLAMF6 double negative cells were found within mature CD24\u2212CD73+ and CD24\u2212CD73\u2212 subsets. In the periphery, SLAMF1 and SLAMF6 expression distinguished IL-17\u2013 and IFN-\u03b3\u2013producing \u03b3\u03b4 T cells, respectively. Disruption of SLAM family receptor signaling through deletion of SAP resulted in impaired thymic V\u03b31 and V\u03b34 T cell maturation at the CD24+CD73\u2212SLAMF1+SLAMF6+ double positive stage that was associated with a decreased frequency of CD44+ROR\u03b3t+ \u03b3\u03b4 T cells. Impaired development was in turn associated with decreased \u03b3\u03b4 T cell IL-17 and IFN-\u03b3 production in the thymus as well as in peripheral tissues. The role for SAP was subset-specific, as V\u03b31V\u03b46.3, V\u03b34, V\u03b35, but not V\u03b36 subsets were SAP-dependent. Together, these data suggest that the SLAM\/SAP signaling pathway plays a larger role in \u03b3\u03b4 T cell development than previously appreciated and represents a critical checkpoint in the functional programming of both IL-17\u2013 and IFN-\u03b3\u2013producing \u03b3\u03b4 T cell subsets.<\/jats:p>","DOI":"10.4049\/jimmunol.1901082","type":"journal-article","created":{"date-parts":[[2020,2,5]],"date-time":"2020-02-05T15:45:52Z","timestamp":1580917552000},"page":"1521-1534","source":"Crossref","is-referenced-by-count":22,"title":["Critical Role for SLAM\/SAP Signaling in the Thymic Developmental Programming of IL-17\u2013 and IFN-\u03b3\u2013Producing \u03b3\u03b4 T Cells"],"prefix":"10.1093","volume":"204","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9380-4873","authenticated-orcid":false,"given":"Oliver","family":"Dienz","sequence":"first","affiliation":[{"name":"Department of Surgery, Larner College of Medicine, University of Vermont , Burlington, VT 05405"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria L","family":"DeVault","sequence":"additional","affiliation":[{"name":"Department of Surgery, Larner College of Medicine, University of Vermont , Burlington, VT 05405"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shawn C","family":"Musial","sequence":"additional","affiliation":[{"name":"Department of Surgery, Larner College of Medicine, University of Vermont , Burlington, VT 05405"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2139-6927","authenticated-orcid":false,"given":"Somen K","family":"Mistri","sequence":"additional","affiliation":[{"name":"Department of Surgery, Larner College of Medicine, University of Vermont , Burlington, VT 05405"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Mei","sequence":"additional","affiliation":[{"name":"Department of Surgery, Larner College of Medicine, University of Vermont , Burlington, VT 05405"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandr","family":"Baraev","sequence":"additional","affiliation":[{"name":"Department of Surgery, Larner College of Medicine, University of Vermont , Burlington, VT 05405"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8031-5381","authenticated-orcid":false,"given":"Julie A","family":"Dragon","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, University of Vermont , Burlington, VT 05405"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2709-7466","authenticated-orcid":false,"given":"Dimitry","family":"Krementsov","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Health Sciences, University of Vermont , Burlington, VT 05405"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andre","family":"Veillette","sequence":"additional","affiliation":[{"name":"Montreal Clinical Research Institute , Montreal, Quebec H2W 1R7 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2673-9148","authenticated-orcid":false,"given":"Jonathan E","family":"Boyson","sequence":"additional","affiliation":[{"name":"Department of Surgery, Larner College of Medicine, University of Vermont , Burlington, VT 05405"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,3,15]]},"reference":[{"key":"2025030417511106000_r1","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1146\/annurev-immunol-032713-120216","article-title":"\u03b3\u03b4 T cells: first line of defense and beyond","volume":"32","author":"Chien","year":"2014","journal-title":"Annu. 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