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Project

The beta-cell and the immune system in type 1 diabetes: partners in crime - developing new therapies in type 1 diabetes through better understanding of beta-cell behaviour and use of novel immunomodulators.

Prevention of type 1 diabetes (T1D), the most common metabolic disease in childhood and adolescence, remains an elusive goal, with therapy after therapy failing to demonstrate long-term efficacy in arresting the autoimmune attack against the pancreatic insulin-producing beta-cell in people at risk for or with recent T1D. We propose to pursue an integrated approach, recognizing the crucial role of both the immune system and the beta-cell in the pathophysiology and natural history of the disease. Our hypothesis is that besides the (auto)-immune system the beta-cell itself is a dynamic partner in the T1D disease process. We believe that this partner should not be neglected when considering new strategies for intervention and disease prevention. The beta-cell is the key as a renewable source of new beta-cells, a provider of beta-cell antigens, a potential source of chemokine production and as a target not only for cell death, but also for dysfunction in the presence of inflammation and immune attack. We recognize moreover the role of the environment, in particular nutrition, in determining immunogenicity, function, and survival of the beta-cell under immune attack. In the present project we want to exploit our expertise in transcriptomics, proteomics, preclinical animal models of T1D and clinical immune interventions to gain further insight into the destructive interaction between the beta-cell and the immune system in T1D. Exchanges of findings between different work packages is maximized, as is cross-fertilization between techniques and expertise in our diverse consortium, consisting of beta-cell physiologists, nutritionists, immunologists, hormone (vitamin D) specialists, T1D animal model specialists, and clinicians, with experience in immune interventions in T1D patients. We have brought together this diverse consortium to realize our objective: To develop novel therapies to stop T1D through a better understanding of beta-cell behavior and the use of novel immunomodulators.
Date:1 Oct 2013 →  30 Sep 2018
Keywords:Diabetes type 1, Beta-cells, Vitamin D, Environment, Antigen therapy
Disciplines:Laboratory medicine, Palliative care and end-of-life care, Regenerative medicine, Other basic sciences, Other health sciences, Nursing, Other paramedical sciences, Other translational sciences, Other medical and health sciences