Gas6/TAM axis in sepsis: Time to consider its potential role as a therapeutic target

Tyrosine kinase receptors are transmembrane proteins involved in cell signaling and interaction. Among them, the TAM family (composed by Tyro 3, Axl, and Mer) represents a peculiar subgroup with an important role in many physiological and pathological conditions. Despite different mechanisms of activation (e.g., protein S and Galactin-3), TAM action is tightly related to their common ligand, a protein named growth arrest-specific 6 (Gas6). Since the expression of both TAM and Gas6 is widely distributed among tissues, any alteration of one of these components can lead to different pathological conditions. Moreover, as they are indispensable for homeostasis maintenance, in recent years a growing interest has emerged regarding their role in the regulation of the inflammatory process. Due to this involvement, many authors have demonstrated the pivotal role of the Gas6/TAM axis in both sepsis and the sepsis-related inflammatory responses. In this narrative review, we highlight the current knowledge as well as the last discoveries on TAM and Gas6 implication in different clinical conditions, notably in sepsis and septic shock. Lastly, we underline not only the feasible use of Gas6 as a diagnostic and prognostic biomarker in certain systemic acute conditions but also its potential therapeutic role in these life-threatening diseases.