New Insights into the Role of Tyro3, Axl, and Mer Receptors in Rheumatoid Arthritis

Figure 1

Model of TAM receptors and ligands’ effects in synovial tissue. Axl and Mer, once activated by their cognate ligands, exert a protective role within the joint by reducing the production of proinflammatory cytokines, such as TNF and IL-6, and triggering the phagocytosis of apoptotic cells. Axl, specifically, also contributes to form a barrier on the synovial lining while Mer further enhances the anti-inflammatory response by upregulating IL-10. Axl is negatively regulated by miR-34a, which is constitutively activated in RA DCs, and can be cleaved and released as soluble (s) Axl in the joint space by proteinases like ADAM10/17. In contrast, Tyro3 may foster synovial hypertrophy of fibroblast-like-synoviocytes (FLS) and increase bone loss.