Factors Defining T Cell Mediated Immunopathology in Psoriasis. (360G-Wellcome-078173_Z_05_Z)

Psoriasis is a significant and common human immunopathology. T cells are thought to play a crucial role as disease effectors, however, factors defining T cell mediated immunopathology during disease development are poorly understood. To be able to address important outstanding scientific questions related to psoriasis pathogenesis, we have developed a novel psoriasis disease model. It represents one of the first available spontaneous human inflammatory disease models. It therefore provides for the first time the basis for the investigation of critical events in early psoriasis development and initiation of T cell mediated immunopathology. We hypothesize that T cell activation and proliferation in psoriasis is dependent on factors such as the local tissue environment, cytokines and resident antigen-presenting cells. We propose to investigate initiation and maintenance of tissue pathology with the following Key Goals: 1. Define the role of local tissue for T cell mediated immunopathology 2. Define the phenotype, function and T cell receptor repertoire of lesional T cells 3. Define key cytokines driving T cell mediated immunopathology The definition of factors involved in T cell mediated immunopathology in psoriasis will broaden our understanding and will also provide new therapeutic targets for of a common human inflammatory disease.