Up-regulation ofproinflammatory cytokines by activated macrophages (Mψ) has been shown to drive the pathogenesis of several rheumatic diseases including rheumatoid arthritis,chronic plaque psoriasis,and psoriatic arthritis,most likely via direct cell-cell contact through immunological synapse (IS) mechanisms in the skin and joints.Our drug discovery research is focused on identifying human T cell and Mψ proteins that mediate adaptive immunity but leave innate immunity intact.Functional proteomics including differential two-dimensional gel electrophoresis using stimulated and non-stimulated human T cells,obtained from healthy human donors or from psoriasis/RA patients with newly diagnosed skin inflammation,were used to select upregulated protein candidates for subsequent identification by tandem mass spectrometry.