The vitamin D system in autoimmune diabetes: unraveling the basis for protection.

Evidence for a role of vitamin D and its metabolites in the pathogenesis of type 1 diabetes (T1D) is accumulating. My promoter, Prof. C. Mathieu, has shown that high doses of active vitamin D,  1,25- dihydroxyvitamin D3 (1,25(OH)2D3), prevent T1D in non-obese diabetic (NOD) mice, a mouse model for human T1D. In order to come to an effective prevention or treatment for T1D, it is of paramount importance to unravel the molecular pathways induced by vitamin D and its metabolites in the immune system. The objective of the present study is to expand our knowledge on the direct immune effects of 1,25(OH)2D3 and its less-calcemic analogues in dendritic cells (first aim) and T cells (second aim) at a molecular level. In a third aim we will investigate the molecular mechanisms responsible for regulation of CYP27B1, the enzyme expressed in antigen presenting cells of the immune system and responsible for the final activation of 1,25(OH)2D3, by 1,25(OH)2D3 itself and its possible role in vitamin D metabolism and risk for developing T1D (third aim).