Autoimmune Vitiligo: gene-expression during pathogenesis

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DESCRIPTION (provided by applicant): Vitiligo is a common acquired hypopigmentary disorder characterized by a loss of epidermal melanocytes. Although the pathogenesis of vitiligo is poorly understood, evidence suggests that in many cases vitiligo is an autoimmune disorder and melanocyte loss is the result of an immunological response. The Smyth line (SL) chicken is an excellent animal model for autoimmune vitiligo that recapitulates the entire spectrum of clinical and biological manifestations of the human disease. The onset and incidence of SL vitiligo (SLV) is predictable, the lesion is easily accessible and the target tissue regenerates, thus providing opportunity to study the evolving lesion prior to and throughout the development of SLV in the same individual. The degeneration of SL melanocytes is preceded by aberrant melanocyte activities that are not sufficient to cause vitiligo without a functioning immune system but do appear to be involved in provoking an immune response resulting in the destruction of melanocytes. Loss of melanocytes in the feather is associated with infiltration of lymphocytes and cell-mediated immune activity, including T helper cells, cytotoxic T cells, IFN- g, and apoptosis. Lastly, an environmental factor, i.e. turkey herpesvirus (HVT), is known to play a role in the development of this disorder. It is the goal of this research proposal to study the local environment in the target tissue (feathers) prior to and throughout the development of SLV. More specifically, to determine the expression of chemokines, cytokines, melanocyte function-associated proteins, heat shock proteins, and pro-/anti-apoptotic proteins, as well as, the presence, state (latent or productive) and viral load of HVT. A time course approach, employing real-time quantitative RT-PCR and immunoblotting, will be used to examine these aspects prior to and throughout the development of SLV. By studying the activities and responses of cells in the target tissue, prior to and throughout the development of SLV, much will be learned about mechanisms involved in the immunopathology of vitiligo and other autoimmune diseases.