Dissection of SAP-dependent and SAP-independent SLAM family signaling in NKT cell development and humoral immunity

Shasha Chen, Chenxu Cai, Zehua Li, Guangao Liu, Yuande Wang, Marzenna Blonska, Dan Li, Juan Du, Xin Lin, Meixiang Yang, Zhongjun Dong

Research output: Contribution to journalArticle

18 Scopus citations


Signaling lymphocytic activation molecule (SLAM)-associated protein (SAP) mutations in X-linked lymphoproliferative disease (XLP) lead to defective NKT cell development and impaired humoral immunity. 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.

Original languageEnglish (US)
Pages (from-to)475-489
Number of pages15
JournalJournal of Experimental Medicine
Issue number2
StatePublished - 2017


ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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