Harnessing the vitamin D system for the prevention and treatment of type 1 diabetes.

Dendritic cells (DC) are considered central immune targets of vitamin D metabolites. In a first aim, we will explore the effects of active vitamin D, 1,25-(OH)2D3, and the structural analogue TX527 on mouse and human DC behaviour and protein profile. In the second aim, we will explore the direct effects of 1,25-(OH)2D3 and TX527 on T lymphocytes. Until now, data on direct effects on T cells are scarce and most authors claim that the alterations in T-cell behaviour (like regulator-cell induction) are mainly the result of DC effects. We will explore the direct effects of the agents on mouse and human T lymphocytes on a functional level, on cell surface markers, cytokine and chemokine production and on a molecular level by micro-array and proteomics approaches. Finally, in a third aim, we will move to the translational level, and explore the potential of combining vitamin D analogues with an anti-T lymphocyte agent, anti-CD3, and with an antigen-specific intervention, exploiting Lactococcus lactis (L. lactis) as carrier for insulin (-peptides).

Keywords:antigen-specific, diabetes, T cells, dendritic cells, vitamine D

Disciplines:Immunology, Endocrinology and metabolic diseases