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Because of the redundancy of SLAM family receptors (SFRs) and the complexity of SAP actions, how SFRs and SAP mediate these processes remains elusive. Here, we examined NKT cell development and humoral immunity in mice completely deficient in SFR. We found that SFR deficiency severely impaired NKT cell development. In contrast to SAP deficiency, SFR deficiency caused no apparent defect in follicular helper T (TFH) cell differentiation. Intriguingly, the deletion of SFRs completely rescued the severe defect in TFH cell generation caused by SAP deficiency, whereas SFR deletion had a minimal effect on the defective NKT cell development in SAP-deficient mice. These findings suggest that SAP-dependent activating SFR signaling is essential for NKT cell selection; however, SFR signaling is inhibitory in SAP-deficient TFH cells. Thus, our current study revises our understanding of the mechanisms underlying T cell defects in patients with XLP.<\/jats:p>","DOI":"10.1084\/jem.20161312","type":"journal-article","created":{"date-parts":[[2017,1,3]],"date-time":"2017-01-03T15:05:11Z","timestamp":1483455911000},"page":"475-489","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":49,"title":["Dissection of SAP-dependent and SAP-independent SLAM family signaling in NKT cell development and humoral immunity"],"prefix":"10.1084","volume":"214","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6067-3966","authenticated-orcid":true,"given":"Shasha","family":"Chen","sequence":"first","affiliation":[{"name":"Institute for Immunology and School of Medicine, Tsinghua University, Beijing 100086, China 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenxu","family":"Cai","sequence":"additional","affiliation":[{"name":"Institute for Immunology and School of Medicine, Tsinghua University, Beijing 100086, China 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6342-3324","authenticated-orcid":true,"given":"Zehua","family":"Li","sequence":"additional","affiliation":[{"name":"Institute for Immunology and School of Medicine, Tsinghua University, Beijing 100086, China 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangao","family":"Liu","sequence":"additional","affiliation":[{"name":"Biomedical Translational Research Institute, Jinan University, Guangzhou 510632, China 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuande","family":"Wang","sequence":"additional","affiliation":[{"name":"Biomedical Translational Research Institute, Jinan University, Guangzhou 510632, China 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5237-8732","authenticated-orcid":true,"given":"Marzenna","family":"Blonska","sequence":"additional","affiliation":[{"name":"Department of Medicine, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL 33136 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3215-8262","authenticated-orcid":true,"given":"Dan","family":"Li","sequence":"additional","affiliation":[{"name":"Institute for Immunology and School of Medicine, Tsinghua University, Beijing 100086, China 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Du","sequence":"additional","affiliation":[{"name":"Institute for Immunology and School of Medicine, Tsinghua University, Beijing 100086, China 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Lin","sequence":"additional","affiliation":[{"name":"Institute for Immunology and School of Medicine, Tsinghua University, Beijing 100086, China 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meixiang","family":"Yang","sequence":"additional","affiliation":[{"name":"Biomedical Translational Research Institute, Jinan University, Guangzhou 510632, China 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2673-4200","authenticated-orcid":true,"given":"Zhongjun","family":"Dong","sequence":"additional","affiliation":[{"name":"Institute for Immunology and School of Medicine, Tsinghua University, Beijing 100086, China 1"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2017,1,3]]},"reference":[{"key":"2023072609213612300_bib1","doi-asserted-by":"publisher","first-page":"5448","DOI":"10.4049\/jimmunol.180.8.5448","article-title":"ICOS\/ICOSL interaction is required for CD4+ invariant NKT cell function and homeostatic survival","volume":"180","author":"Akbari","year":"2008","journal-title":"J. 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