Lymphocytes are central for the regulation of an immune response. CD4+ T lymphocytes can differentiate to functionally distinct subsets and classified based on their cytokine secretion profiles as well as other properties. Proper regulation and balance between various lymphocyte subsets is central for the appropriate function of the immune system and required e.g. for host defence against pathogens or cancer as well as protection from autoimmune diseases. Recently, a new effector CD4+ T cell subset Th17 was discovered and named according to the main cytokine they secrete, IL17. Besides being involved in host defence to extracellular pathogens, Th17 cells play a central role in the pathogenesis of inflammatory diseases in human and experimental mouse models. The recent discovery by the Stockinger group links the aryl hydrocarbon receptor, a transcription factor widely studied in the toxicology field, and the Th17 system, which provides new hypotheses on the potential mechanisms underlying the well-established connection between the environmental factors and autoimmune diseases. The cellular response to an external stimulus is mediated through a series of overlapping networks that include the signalling network, the epigenetic and transcription factor control mechanisms at genome level, and the gene regulatory. In this project we will study these control mechanisms during the differentiation of Th17 cells by combining genome-wide experimental and computational approaches. We expect that our project results in the identification of the key regulatory components of each of the networks involved, as well as provide insights into the nature of molecular interactions between them. Such regulatory hubs, or the pathways that they participate in, provide targets for rational chemotherapy either for the immune-mediated diseases described above, or for enhancing protective immunity against infectious agents. Our multidisciplinary consortium provides cutting-edge complementary expertise to achieve the goals.