"We propose a multidisciplinary “translational research” project that will exploit the molecular and cellular features of innate immunity potentially involved in the pathogenesis of autoimmune diseases in humans. Given the significant scientific advances over the past years in characterizing the physiology of cells from the innate immune system, we will attempt to identify the role of natural killer (NK) cells and dendritic cells (DCs) in the physiopathology of various autoimmune disorders. Combining different professional expertise in clinical and basic immunology, we plan the following: 1) To select cohorts of patients affected by several systemic autoimmune diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), systemic sclerosis (scleroderma) and other various forms of vasculitis. We will conduct our investigations on both naive untreated patients with active disease and patients undergoing immuno-suppressive therapy with disease in remission, in either cross-sectional or longitudinal studies 2) To collect total peripheral blood lymphocytes through either blood draws or leukapheresis procedures in order to obtain large numbers of cells for analysis. 3) To identify significant aberrancies in the phenotype and functions of NK cells and DCs that may further our understanding of the physiopathology of autoimmunity. 4) To better understand how innate and adaptive immunity are linked and whether aberrant interactions between the two arms of the immune system lead to the lack of immunological tolerance in autoimmune disorders, in order to develop alternative therapeutic approaches to autoimmune disorders 5) To develop new diagnostic tools that better characterize the status of innate immune competent cells and improve classification of the stages of autoimmune disorders, which could lead to a more effective use of immunosuppressive agents."