Diabetes fonds Ruby Grant 275 kE for department of TIL

Schulte, Barbara

Prof. Gosse Adema and Dr. Barbara Schulte of the Department of Tumor Immunology NCMLS  received a Diabetes Fonds Ruby Grant (275 kE).

The work will be performed in collaboration with Frank van Kuppeveld

Title of Research:

Mimicking the onset of autoimmune type 1 diabetes: Enterovirus-infected pancreatic β-cells, primary human dendritic cells and innate lymphocytes.

Abstract

Type 1 diabetes mellitus (T1D) is an autoimmune disorder in which the insulin-producing β-cells in the pancreas are destroyed. Enterovirus infections are associated with the development of T1D. A causal relationship has been implicated, yet formal proof is lacking, as well as the underlying mechanism. Dendritic cells (DCs) are the major antigen-presenting cells (APCs) and exert a dual function: they initiate immune responses against pathogens or tumors, but also prevent (auto-)immune responses harmful to the host. Their decisive role in immunity and tolerance causes these cells to play a crucial role in the pathogenesis of autoimmune diseases like T1D.

We hypothesize that enterovirus-infected β-cells that are phagocytosed by DCs can unleash the immune system and eventuate in autoimmunity in genetically susceptible individuals. We will study the interplay between different human primary DC subsets - each playing their own distinct role in the human immune system - and enterovirus infected β-cells. We will investigate how cross-talk between distinct DC subsets and other immune cells influences the outcome of the immune response at the functional and molecular pathway level. We aim to study the differences in selected pathways important in the DC's response to enterovirus-infected β-cells between healthy individuals and T1D patients. We envisage that a detailed understanding of which cells, and how they are involved in initiation of (auto-)immunity, will be instrumental for optimal design of novel T1D intervention strategies.


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