Novel regulators of immune responses
The differentiation of helper T lymphocytes (Th0) into Th1 cells is mediated by IL-12 and is central for subsequent cell-mediated immune responses against intracellular pathogens. The proprotein convertase (PC) furin has been identified as an IL-12 target gene. It has been associated with the pathogenesis of several diseases, including metastatic cancers, cystic fibrosis and infectious diseases. PC is implicated in the activation of various proteins by removing amino acid chains that may block protein activity. Funded by the EU, the 'Proprotein convertase furin as a regulator of immune responses' (FURIN IN IMMUNITY) project concentrated on the physiological role of furin in immunity. Research will elucidate the molecular mechanisms of the furin function in T cells as well as delineate its role in innate responses and immune-mediated diseases. Scientists studied furin-deficient mice and found an unexpected loss of peripheral tolerance and the development of autoimmune disease. Microarray analysis was then used to investigate the signalling pathways in T cells that are orchestrated by furin. Furin was also found to be up-regulated in atherosclerotic plaques alongside many of its target molecules. Ongoing work is concentrated on providing genetic links between furin and atherosclerosis, as well as on deciphering furin deregulation in autoimmunity. Furthermore, by using zebrafish and fruitfly furin models, researchers hope to provide evidence on the physiological role of furin in hematopoiesis and immune function. FURIN IN IMMUNITY studies have implicated furin in various immune-mediated diseases. Further studies and elucidation of molecular mechanisms could lead to the identification of novel disease-associated biomarkers and to the development of therapeutic PC inhibitors.
