UC San Diego

Little is understood about the genesis of autoimmune diseases caused by deficiencies in TAM receptors (Tyro3, Axl, Mer). One of the causes of autoimmunity could be defective thymic education. Our goal was to elucidate the localization and role of TAM receptors and their ligands within the thymus. We show that Axl and Mer, but not Tyro3, are expressed within the thymus. Through immunohistochemistry, we identify Axl and Mer expression primarily on macrophages in both the medulla and cortex. Using knockout mice, we show that Axl and Mer perform necessary but redundant roles in the elimination of basally accumulated apoptotic thymocytes. The absence of both receptors leads to immense apoptotic cell accumulation within thymic cortex and medulla.These changes result in minor morphological defects as the weight but not the ratio of medulla to cortex was affected in the Axl-/-Mertk-/- mice. We further use this model to instigate Axl dependence on Gas6 as a ligand in thymus. Additionally, we show that during acute thymocyte apoptosis, Mer but not Axl is critical in cellular clearance.