Dr. Zhongjun Dong and colleagues reported their findings on NKT cell development and function in the Journal of Experimental Medicine, titled "Dissection of SAP-dependent and SAP-independent SLAM family signaling in NKT cell development and humoral immunity".

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, they examined NKT cell development and humoral immunity in mice completely deficient in SFR, and 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, the published study revises our understanding of the mechanisms underlying T cell defects in patients with XLP.

The graduate students Shasha Chen, Chenxu Cai, and Zehua Li are co-first authors of this publication. This work was partially supported by grants from the National Natural Science Foundation of China, Ministry of Science and Technology and Tsinghua-Peking Center for Life Sciences.

The original paper could be found in the following link:

http://jem.rupress.org/content/early/2016/12/30/jem.20161312