This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The TAM family of receptor tyrosine kinases participates in both innate and adaptive immune response. Mice lacking all three receptors exhibit defective clearance of apoptotic cells or spent cellular organelles by the professional or non-professional phagocytes. Apoptotic cells are a major source of autoantigens and impaired clearance leads to the development of autoimmunity. Furthermore, Axl and Mertk, two members of TAM family, are expressed by macrophage and dendritic cells (DC), and play a negatively regulatory role during the antigen-presenting cell (APC) activation. Overpresentation of autoantigens in the mutant APCs causes autoimmune disorders. We have previously shown that TAM triple (as well as AM double) mutants produce elevated levels of circulating autoantibodies, overreactive ocular antigen-specific syngeneic T-cell population. In this period of study, we further demonstrated that AM double (also triple) mutant mice developed ocular autoimmune disorder through overwhelmingly hyperactivation of Th1 subtype of T cells. This study brings us even closer to understanding of the molecular etiology for human uveitis.
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