TAM receptor signaling and autoimmune disease

The TAM receptor tyrosine kinases Tyro3, Axl, and Mer and their ligands Gas6 and Protein S are essential for the phagocytosis of apoptotic cells and membranes in the adult immune, nervous, and reproductive systems. Genetic studies indicate that this receptor-ligand system is central to apoptotic cell engulfment that is triggered by the ‘eat-me’ signal phosphatidylserine (PtdSer). At the same time, TAM signaling is normally activated by Toll-like receptor (TLR) and type I interferon signaling, as part of the innate inflammatory response in dendritic cells (DCs) and macrophages, where it inhibits this response. Deficiencies in TAM signaling result in human retinal dystrophies and may contribute to lupus and other human autoimmune diseases.