Treg Vaccination in Autoimmune Type 1 Diabetes

Foxp3⁺ regulatory T (Treg) cells are critical contributors to the establishment and maintenance of immunological self-tolerance. Autoimmune type 1 diabetes (T1D) is characterized by the loss of self-tolerance to the insulin-producing β cells in the pancreas and the destruction of β cells, resulting in the development of chronic hyperglycemia at diagnosis. The application of strong-agonistic T-cell receptor ligands provided under subimmunogenic conditions functions as a critical means for the efficient de novo conversion of naive CD4⁺ T cells into Foxp3⁺ Treg cells. The specific induction of Treg cells upon supply of strong-agonistic variants of certain self-antigens could therefore function as a critical instrument in order to achieve safe and specific prevention of autoimmunity such as T1D via the restoration of self-tolerance. Such immunotherapeutic strategies are being developed, and in the case of T1D aim to restrict autoimmunity and β-cell destruction. In this review, we discuss the requirements and opportunities for Treg-based tolerance approaches with the goal of interfering with autoimmune T1D.     

Genetische Ätiologie bei chronisch-entzündlichen Darmerkrankungen

Crohn’s disease and ulcerative colitis are the two main forms of inflammatory bowel disease. Inflammatory bowel diseases have a life time prevalence of up to 1?% in western industrialized countries. It is generally proposed that genetic susceptibility, which is much more widespread in the population, needs (unknown) factors in lifestyle in order to lead to disease manifestation. Systematic genome-wide association studies opened a new level of understanding of the risk architecture of inflammatory bowel diseases. This has led to the concept that barrier problems on the level of the intestinal epithelial cells may be a main driver in disease etiopathogenesis. Many of the newly discovered disease genes are not only relevant for inflammatory bowel disease but also for other disorders. This has initiated a large research interest in co-morbidities, which appear to be overlooked on the clinical side, too. Novel therapies should address the primary disease mechanisms and therefore provide causal interventions. Endpoints should include the avoidance of co-morbidities, which may be a limiting factor for patients with chronically active disease.