Diversification of TAM receptor function

Abstract

Apoptotic cell clearance is critical for both tissue homeostasis and the resolution of inflammation. We found that the TAM receptor tyrosine kinases Axl and Mer played distinct roles as phagocytic receptors in these two settings, where they exhibited divergent expression, regulation, and activity. Mer acted as a tolerogenic receptor in resting macrophages and in settings of immune suppression. Conversely, Axl was an inflammatory response receptor whose expression was induced by pro-inflammatory stimuli. Axl and Mer displayed distinct ligand specificities, ligand-receptor complex formation in tissues, and receptor shedding upon activation. These differences notwithstanding, phagocytosis by either protein was strictly dependent on receptor activation that was triggered by bridging TAM receptor–ligand complexes to the ‘eat-me’ signal phosphatidylserine on apoptotic cell surfaces.