Genetic basis of autoimmune pancreatitis

Autoimmune pancreatitis (AIP) represents a rare but clinically important variant of chronic pancreatitis. From a clinical point of view, research on AIP is motivated by both the diagnostic difficulties to distinguish between AIP and pancreatic cancer, and the specific therapeutic consequences for AIP patients. In addition, the immunological mechanisms involved in AIP pathogenesis are of basic interest, e.g. since immunological processes play a role in the progression of more frequent forms of pancreatitis as well. The principle goal of the project is a systematic analysis of the genetic basis of AIP in a murine model of the disease. In previous work, the applicants have established a stable mouse breeding line (termed advanced intercross line; AIL) by crossbreeding an AIP-susceptible mouse strain with AIP resistant lines. By means of genotyping and phenotyping, quantitative trait loci were mapped that are associated with the disease. The proposed project aims at an identification of candidate genes of AIP (based on next generation sequencing and gene expression data) and their validation in the course of functional studies. Therefore, it is also planned to perform in vitro experiments to elucidate mechanisms of AIP progression. Specific investigations that are based on the already available results include studies with dendritic cells (cultured alone and together with T-cells) and the characterization of autoreactive T-cells. In addition, human samples will be included into the investigations. In the long run, the results of the project are also expected to contribute to the establishment of novel markers for AIP diagnostics.