Therapeutic potential of TAM receptors in autoimmune diseases: insights from original studies

TAM receptors, composed of Tyro3, Axl, and Mertk, belong to the receptor tyrosine kinase family and are activated by binding of their cognate ligands, Gas6 and Pros1. These receptor-ligand interactions mediate critical physiological processes, including the maintenance of immunological equilibrium, thrombocyte aggregation and subsequent thrombus development, apoptotic cellular debris clearance, homeostatic regulation of endothelial and vascular smooth muscle cells, and erythrocyte production. Perturbations in TAM signaling cascades have been shown to compromise the clearance of apoptotic cells, leading to persistent inflammatory responses that can contribute to the development of various autoimmune pathologies, including multiple sclerosis, rheumatoid arthritis, Sjögren's syndrome, and systemic lupus erythematosus. We retrieved and reviewed only the primary studies addressing the roles of TAM receptors and their ligands in selected autoimmune diseases from Google Scholar, Scopus, Web of Science, and PubMed. The critical roles of TAM receptors in immune homeostasis and apoptotic cell clearance are well established. However, findings from several primary studies discussed in this review further emphasized that the loss of TAM receptor function in these processes significantly contributes to the pathogenesis and progression of autoimmune diseases. Herein, we highlight the role of TAM receptors in several autoimmune diseases, suggesting that TAM receptors are potential biomarkers for monitoring disease prognosis and therapeutic targets to improve patient outcomes.