From pathogenesis to therapeutic targeting: new insight into TAM receptors in rheumatoid arthritis.

Rheumatoid arthritis (RA), a systemic autoimmune disorder driven by chronic joint inflammation and progressive tissue damage, is orchestrated by a complex interplay of immune cells and signaling pathways. Among these, the TAM receptor family, comprising Tyro3, Axl, and MerTK, has emerged as a critical regulator of immune homeostasis and inflammatory resolution. Activation of TAM receptors by their cognate ligands helps restore tissue integrity through key mechanisms including the suppression of innate immune cell activation, enhancement of apoptotic cells (ACs) clearance, and promotion of tissue repair. Given these multifaceted roles, the TAM signaling pathway presents a compelling therapeutic target for RA. This review systematically delineates the biological rationale for targeting TAM receptors in RA, explores their potential as diagnostic biomarkers, and evaluates the current landscape of TAM-directed therapeutics. Ultimately, targeting the TAM axis offers a promising avenue to refine clinical management strategies for RA.