{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T04:46:14Z","timestamp":1789879574965,"version":"4.0.1"},"reference-count":73,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2014,12,1]],"date-time":"2014-12-01T00:00:00Z","timestamp":1417392000000},"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":[[2014,12,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>IL-17 plays critical roles in host defenses, combating bacterial and fungal infections, as well as the pathogenesis of autoimmune diseases such as experimental autoimmune encephalomyelitis (EAE). The signaling adaptor SAP is essential for normal immune homeostasis and mutations within SH2D1A, the locus encoding this protein, result in serious and sometimes fatal syndromes, including X-linked lymphoproliferative disease and severe cases of common variable immunodeficiency. However, the precise cellular basis of how SAP deficiency contributes to immune dysfunction remains incompletely understood. In this study, we found that CD4 and CD8 T cells lacking SAP had a diminished capacity to differentiate into IL-17\u2013producing Th17 and T cytotoxic (Tc17) cells relative to wild-type lymphocytes. The use of costimulating SLAM Abs was found to augment the differentiation of IL-17\u2013secreting effectors in wild-type but not Sh2d1a\u2212\/\u2212 splenic T cells under IL-17\u2013polarizing conditions. In addition, SAP\u2019s regulation of IL-17\u2013secreting T cells was shown to be a T cell\u2013intrinsic role, as purified naive Sh2d1a\u2212\/\u2212 CD4 and CD8 T cells were inherently defective at converting into Th17 and Tc17 cells in vitro and in vivo. Furthermore, Sh2d1a\u2212\/\u2212 mice were protected from EAE and exhibited greatly decreased numbers of CNS-infiltrating Th17 and Tc17 effector T cells and reduced disease severity. Collectively, these results suggest that SLAM\u2013SAP signaling drives the differentiation and function of Th17 and Tc17 cells in vitro and in vivo and contributes to the pathogenesis of autoimmunity in EAE.<\/jats:p>","DOI":"10.4049\/jimmunol.1301435","type":"journal-article","created":{"date-parts":[[2014,11,1]],"date-time":"2014-11-01T08:54:25Z","timestamp":1414832065000},"page":"5841-5853","source":"Crossref","is-referenced-by-count":11,"title":["SLAM\u2013SAP Signaling Promotes Differentiation of IL-17\u2013Producing T Cells and Progression of Experimental Autoimmune Encephalomyelitis"],"prefix":"10.1093","volume":"193","author":[{"given":"Yu-Hsuan","family":"Huang","sequence":"first","affiliation":[{"name":"Child and Family Research Institute, BC Children\u2019s Hospital , Vancouver, British Columbia V5Z 4H4 ,","place":["Canada"]},{"name":"Department of Pathology and Laboratory Medicine, University of British Columbia , Vancouver, British Columbia V5Z 4H4 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Tsai","sequence":"additional","affiliation":[{"name":"Child and Family Research Institute, BC Children\u2019s Hospital , Vancouver, British Columbia V5Z 4H4 ,","place":["Canada"]},{"name":"Department of Pathology and Laboratory Medicine, University of British Columbia , Vancouver, British Columbia V5Z 4H4 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caixia","family":"Ma","sequence":"additional","affiliation":[{"name":"Child and Family Research Institute, BC Children\u2019s Hospital , Vancouver, British Columbia V5Z 4H4 ,","place":["Canada"]},{"name":"Division of Gastroenterology, Department of Pediatrics, University of British Columbia , Vancouver, British Columbia V5Z 4H4 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce A","family":"Vallance","sequence":"additional","affiliation":[{"name":"Child and Family Research Institute, BC Children\u2019s Hospital , Vancouver, British Columbia V5Z 4H4 ,","place":["Canada"]},{"name":"Division of Gastroenterology, Department of Pediatrics, University of British Columbia , Vancouver, British Columbia V5Z 4H4 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John J","family":"Priatel","sequence":"additional","affiliation":[{"name":"Child and Family Research Institute, BC Children\u2019s Hospital , Vancouver, British Columbia V5Z 4H4 ,","place":["Canada"]},{"name":"Department of Pathology and Laboratory Medicine, University of British Columbia , Vancouver, British Columbia V5Z 4H4 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rusung","family":"Tan","sequence":"additional","affiliation":[{"name":"Child and Family Research Institute, BC Children\u2019s Hospital , Vancouver, British Columbia V5Z 4H4 ,","place":["Canada"]},{"name":"Department of Pathology and Laboratory Medicine, University of British Columbia , Vancouver, British Columbia V5Z 4H4 ,","place":["Canada"]},{"name":"Department of Pathology, Sidra Medical and Research Center , Doha ,","place":["Qatar"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2014,12,15]]},"reference":[{"key":"2025030707505652300_r1","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1111\/j.1600-065X.2010.00951.x","article-title":"Peripheral CD4+ T-cell differentiation regulated by networks of cytokines and transcription factors","volume":"238","author":"Zhu","year":"2010","journal-title":"Immunol. 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