The SLAM family receptors: Potential therapeutic targets for inflammatory and autoimmune diseases

Abstract

The signaling lymphocytic activation molecule (SLAM) family is comprised of nine distinct receptors (SLAMF1 through SLAMF9) that are expressed on hematopoietic cells. All of these receptors, with the exception of SLAMF4, are homotypic by nature as downstream signaling occurs when hematopoietic cells that express the same SLAM receptor interact. The SLAM family receptor function is largely controlled via SLAM associated protein (SAP) family adaptors. The SAP family adaptors consist of SAP, Ewing sarcoma associated transcript (EAT)-2, and EAT-2-related transducer (ERT). These adaptors associate with the cytoplasmic domain of the SLAM family receptors through phosphorylated tyrosines. Defects in SLAM family members and SAP adaptors have been implicated in causing immune deficiencies. This is exemplified in patients with X-linked lymphoproliferative (XLP) disease, where SAP undergoes a loss of function mutation. Furthermore, evidence has been accumulating that SLAM family members are potential targets for inflammatory and autoimmune diseases. This review will discuss the structure and function of the SLAM family receptors and SAP family adaptors, their role in immune regulation, and potential approaches to target this family of receptors therapeutically.

A Human IgSF Cell-Surface Interactome Reveals a Complex Network of Protein-Protein Interactions

“…The signaling lymphocytic activation molecule subfamily (SLAM; 9 members) is expressed on most immune cells ( Dragovich and Mor, 2018 ). SLAMs function as both co-stimulatory and co-inhibitory molecules in innate and adaptive immunity, and play an integral role in autoimmune disorders.…”

Identifying the pattern of immune related cells and genes in the peripheral blood of ischemic stroke

“…In addition, compared with the healthy control group, SLAMF1 was significantly down-regulated in patients with acute myocardial infarction (AMI) [ 28 ]. Evidence has been accumulating that SLAM family members are potential targets for inflammatory and autoimmune diseases [ 29 ]. Bacille Calmette-Guérin (BCG) infection significantly upregulated SLAMF1, which enhanced inflammatory response by activating the NF-κB signaling pathway [ 30 ].…”

Signalling lymphocyte activation molecule family member 9 is found on select subsets of antigen‐presenting cells and promotes resistance to Salmonella infection

“…CD48 and 2B4 interact heterotypically with one another, whereas SLAM, Ly9, CD84, NTB‐A, CRACC, and BLAME are homophilic. References to putative homotypic interactions by SLAMF9 are found in the literature, but the origins of this assumption are unclear, because no published data exist showing self‐association by SLAMF9. In our studies on mouse SLAMF9, no evidence for self‐association was observed by SEC‐MALS (see Supplementary material, Fig. )…”