The impact of B-cells on the fibroinflammatory tissue remodeling during chronic pancreatitis

• Applicant: Privatdozent Dr. Matthias Sendler
• Subject Area: Gastroenterology
• Term: since 2026
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 576085219

Chronic pancreatitis is an inflammatory disease of the pancreas that is associated with a considerable impairment of quality of life and increased morbidity for patients. The course of the disease is characterised by recurrent episodes of acute pancreatitis. After the acute inflammation has subsided, the destroyed exocrine tissue is replaced by fibrosis. During disease progression, the gradual loss of exocrine and endocrine tissue results in functional impairment of the organ. The process of fibrosis is still not well understood and represents a starting point for tissue-preserving therapy. A large number of different cells are involved in the process of fibrosis. In addition to fibroblasts, cells of the innate immune system, such as macrophages, are primarily involved in fibrogenesis. In addition to the cells of the innate immune system also cells of the adaptive immune system, such as T cells, are also involved in this process. In preliminary work, we were able to detect a considerable number of B cells in the chronically inflamed pancreas in addition to T cells in an animal model of chronic pancreatitis. The aim of the project is to investigate the role of B cells during chronic pancreatitis with respect to tissue fibrosis and remodelling of the organ. To study B cells in an animal model of chronic pancreatitis, we will use a mouse model that allows us to deplete B cells in vivo. Mice expressing the inducible diphtheria toxin receptor flanked by LoxP sites will be crossed with mice expressing the Cre recombinase downstream of the CD19 promoter. This enables to deplete CD19+ B cells in vivo by the application of Diphteria toxin in order to investigate their influence on fibrosis in the course of pancreatitis. Furthermore, the signalling pathways of B-cell activation will be characterised in animal and cell culture models in order to identify therapeutic options. Finally, a therapeutic approach will be used to test whether a BAFF (B-cell activating factor) blocking antibody represents a therapeutic option for chronic pancreatitis. In a translational approach we will use human samples to verify whether the data collected in the animal model can be transferred to patients.

• DFG Programme: Research Grants