Effect of hyperglycaemia and glucose concentration on tolerogenic properties of dendritic cells: clues for diabetes associated inflammation

Abstract

Dendritic cells (DCs) are a subtype of cells specialized in antigen capture, processing and presentation, thus triggering the response of T lymphocytes. DCs may generate immunity or tolerance, depending on the extracellular signals they receive. DCs that receive tolerogenic signals, such as 1,25(OH)2D3, are characterized by their ability to generate, , CD4+CD25+FoxP3+ T lymphocytes or to induce an anergic state in CD4+ effector T lymphocytes. When in an immature state, DCs rely on an oxidative phosphorylation (OXPHOS) profile and, once activated, there is a rapid increase in glycolysis, which is believed to be necessary for the functions of activated DCs. The balance between the DC's immunogenic and tolerogenic profile may also be regulated by the metabolic environment these cells are exposed to. Preliminary data suggest that monocytes-derived DCs (mo-DCs) differentiated from hyperglycemic Type 1 diabetes patients, fail to present a full tolerogenic profile induced by 1,25(OH)2D3. This leads us to hypothesize that glucose concentrations dictate the functional properties of tolerogenic DCs, , Therefore the present project aims to better understand the role of glucose during tolerogenic DCs differentiation, not only when induced by 1,25(OH)2D3, but also by other molecules, such as retinoic acid and dexamethasone This may provide new mechanistic insights into why immune responses in diabetes patients are often deregulated.