Assessing the relevance of a target organ specific microRNA signature in type 1 diabetes

Type 1 diabetes (T1D) is an autoimmune disease that results from T cell-mediated destruction due to a breach in immune tolerance toward the insulin-producing β-cells, leading to an absolute insulin deficiency. T1D clinical presentation does not occur until 80–90% of the β-cells have been destroyed, and there is a marked gap between the onset of autoimmunity and the onset of disease. Therefore, new biomarkers are urgently needed in order to monitor T1D progression, but also to predict and assess the efficacy of therapeutic interventions. MicroRNAs (miRNAs) are a class of small non-coding RNAs recently found to be present in biological fluids such as blood and urine. These tiny molecules being extremely stable in biological fluids represent a promising class of prognostic and diagnostic biomarkers in several diseases including autoimmune diabetes. Therefore, the aims/themes of the present PhD are: 1) to investigate miRNAs differentially expressed in pancreas and in blood (plasma) samples of type 1 diabetes model (i.e. non obese diabetic (NOD) mice) progressing or not to disease in order to assess whether circulating miRNAs mirror the phenomena occurring at the level of the target organ, 2) to investigate whether circulating miRNAs can be used as prognostic biomarkers in a previously successfully established antigen-based therapy.