To bring together a consortium of leading European researchers spanning the field from genetics, through pancreatic beta-cells, dendritic cell and T-cell biology towards clinical interventions, allowing the development of novel and logical interventional therapies in Type 1 Diabetes.
We propose to pioneer the concept of tailored interventions with minimal immune system interference in new onset Type 1 Diabetes, leading to beta-cell protection and restoration, based on a solid understanding of the disease pathogenesis, enabling our experimental findings to be adopted for future clinical application.
The specific objectives of the project NAIMIT are:
1. To explore novel immunomodulatory approaches using natural immunomodulators (e.g. antigen, glucocorticoids and vitamin D derivatives) to modulate DC and T-lymphocyte function, both in vitro and in vivo with the aim of inducing antigen-specific regulation.
2. To introduce novel immunomodulatory tools to induce antigen-specific tolerance: soluble monoclonal TCRs (mTCRs) and L. lactis.
3. To gain insight into the mechanisms involved in immune-mediated beta-cell death aimed at harnessing the beta-cell against autoimmune attack.
4. To unravel the means of communication between beta-cells and the immune system in order to interfere with beta-cell destruction and propagation of the beta-cell destruction process.
5. To explore genetic variants responsible for the response to interventions allowing individualised therapies.
6. To build a consortium spanning basic and clinical research to allow new and individualised therapeutic approaches for clinical interventions in T1DM in the future.