More than 5 million people in Europe live with inflammatory bowel disease (IBD) or rheumatoid arthritis (RA). Both diseases are characterized by chronic inflammation partially mediated by inappropriate T cell response. Effector T-cell responses can be modulated by competing positive or negative costimulatory signals, and dysregulated balance between these signals may lead to chronic autoimmune inflammation. In mice, within the CD4+ T cell population, the expression of NKG2D is primarily associated with pathological conditions and the administration of blocking anti-NKG2D antibodies ameliorated the disease in mouse models of arthritis and IBD. Therefore the aim of my project proposal is to clarify the role of NKG2D receptor signalling in CD4+ T cell biology and in the pathogenesis of autoimmune diseases. My work will implement mouse models to study the specific impact of NKG2D expressed on CD4+ T cells in the priming, formation and maintainance of memory of CD4+ T cells and their cytokine profile during homeostasis as well as in preclinical models of IBD and RA. Moreover, by global analysis of human NKG2D+ CD4+ T cells from the sites of inflammation, we aim to better understand the possible role of NKG2D in driving inflammatory responses in IBD and RA patients. By combining these approaches, we intend to get further insights into the role of NKG2D in the regulation of autoimmune diseases and to identify strategies to possibly ameliorate tissue damage and dampen inflammation.
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