Sh2d1b1, also known as EAT-2, is an adaptor protein expressed in innate immune cells such as natural killer (NK) cells. It belongs to the SAP family and is closely related to SAP (SH2D1A). EAT-2 is involved in regulating signaling lymphocyte activation molecule (SLAM)-related receptors, which are crucial for immunomodulation [1,2,3].

Mice lacking or overexpressing EAT-2 were created to study its function in NK cells. Unlike SAP, EAT-2 was found to be an inhibitor of NK cell function, repressing natural cytotoxicity and interferon-γ secretion through tyrosine phosphorylation of its C terminus [3]. In mice lacking SAP, EAT-2 and ERT, the elimination of hematopoietic cells by NK cells was impaired as SLAM receptors lost their activating function and became inhibitory, repressing other activating receptors like NKG2D [4]. In another study, CRACC, a SLAM family receptor, positively regulated NK cell functions in an EAT-2-dependent manner, but was inhibitory in the absence of EAT-2 [5].

In conclusion, Sh2d1b1 (EAT-2) plays a significant role in the regulation of NK cell function, specifically in the surveillance and elimination of hematopoietic cells. The use of gene-knockout mouse models has been crucial in revealing its function in these immune-related processes, providing insights into the mechanisms underlying immune responses and potentially related immune-deficiency diseases [3,4,5].

References:

1. Veillette, André, Latour, Sylvain. . The SLAM family of immune-cell receptors. In Current opinion in immunology, 15, 277-85. doi:. https://pubmed.ncbi.nlm.nih.gov/12787752/

2. Morra, M, Howie, D, Grande, M S, Engel, P, Terhorst, C. . X-linked lymphoproliferative disease: a progressive immunodeficiency. In Annual review of immunology, 19, 657-82. doi:. https://pubmed.ncbi.nlm.nih.gov/11244050/

3. Roncagalli, Romain, Taylor, James E R, Zhang, Shaohua, Latour, Sylvain, Veillette, André. 2005. Negative regulation of natural killer cell function by EAT-2, a SAP-related adaptor. In Nature immunology, 6, 1002-10. doi:. https://pubmed.ncbi.nlm.nih.gov/16127454/

4. Dong, Zhongjun, Cruz-Munoz, Mario-Ernesto, Zhong, Ming-Chao, Latour, Sylvain, Veillette, André. 2009. Essential function for SAP family adaptors in the surveillance of hematopoietic cells by natural killer cells. In Nature immunology, 10, 973-80. doi:10.1038/ni.1763. https://pubmed.ncbi.nlm.nih.gov/19648922/

5. Cruz-Munoz, Mario-Ernesto, Dong, Zhongjun, Shi, Xiaochu, Zhang, Shaohua, Veillette, André. 2009. Influence of CRACC, a SLAM family receptor coupled to the adaptor EAT-2, on natural killer cell function. In Nature immunology, 10, 297-305. doi:10.1038/ni.1693. https://pubmed.ncbi.nlm.nih.gov/19151721/