Modulation of Autoantigen Trafficking and TLR engagement by FcgRIIB and AP3B1

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DESCRIPTION (provided by applicant): Our lab is focused on understanding how pathogenic immune complexes (IC) formed from DNA and/or RNA and antibodies contribute to the pathogenesis of systemic lupus erythematous (SLE). We use in vitro and in vivo models to determine the molecular mechanisms that govern the activation of immune cells by DNA and/or RNA antibody complexes. This particular project is investigating how IC trafficking within immune cells affects the functional outcome. We have developed novel ICs that are also pH sensors. Using these ICs we can rapidly screen the effect of genetic factors and therapeutic agents on IC trafficking in B cells and phagocytes. PUBLIC HEALTH RELEVANCE: The relationship between genetics, environment and the development of autoimmune disease is poorly understood. This application will try to understand how a bona fide susceptibility gene found in systemic lupus erythematous (SLE) patients contributes to the development of autoimmunity. We will maximize the public health impact by testing therapies that are currently in phase II clinical trials in our in vitro and in vvo models of SLE.