Cutaneous and systemic lupus induced by UVB

Studies of lupus mice have contributed little to understanding the basic pathogenesis of skin disease or ultraviolet (UV) light induced precipitation of systemic flares, We propose that this is due both to lesser exposure of mice to UVB as well as fundamental differences in PDC between mice and humans. In this proposal, we have begun to create a new mouse model of UVB mediated skin disease that is associated both with PDC infiltration as well as a type 1 interferon (IFN) signature. Using these conditions of IJVB exposure, we propose to 1) Determine what are the stimuli, sensors and role of PDC following LJVB exposure 2) Create a humanized mouse model of cutaneous LE and determine which autoantibodies are most potent in initiating IFN and inflammation in the skin 3) Develop a systemic mouse model of UVB mediated disease exacerbation using mice that express defined antibodies and Toll Like Receptors that we predict will sensitize mice to IJVB exposure. Successful completion of these Aims will not only inform us of mechanisms responsible for UVB induced lupus but also provide researchers with useful models for trialing therapies.