TY - JOUR
T1 - Dissection of SAP-dependent and SAP-independent SLAM family signaling in NKT cell development and humoral immunity
AU - Chen, Shasha
AU - Cai, Chenxu
AU - Li, Zehua
AU - Liu, Guangao
AU - Wang, Yuande
AU - Blonska, Marzenna
AU - Li, Dan
AU - Du, Juan
AU - Lin, Xin
AU - Yang, Meixiang
AU - Dong, Zhongjun
N1 - Funding Information:
We thank L. Yin for sharing the SAP-deficient mice and Xiaoqian Zhang for help during revision. Work in the Dong laboratory is supported by the Ministry of Science and Technology of China (grant 2013CB944901) and the Natural Science Foundation of China (grants 81322041, 81273198, 81361128016, and 81471523). The authors declare no competing financial interests.
Publisher Copyright:
© 2017 Chen et al.
PY - 2017
Y1 - 2017
N2 - 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.
AB - 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.
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U2 - 10.1084/jem.20161312
DO - 10.1084/jem.20161312
M3 - Article
C2 - 28049627
AN - SCOPUS:85012254480
VL - 214
SP - 475
EP - 489
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
SN - 0022-1007
IS - 2
ER -