Protective function of PDGFR-alpha in intestinal Inflammation

• Applicant: Dr. Carolin Friederike Manthey
• Subject Area: Gastroenterology
• Term: from 2017 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 392653902

The goal of this project is to define the role of PDGFR-alpha in intestinal inflammation and thereby gain insight into pathomechanisms of inflammatory bowel diseases (IBD). PDGFR and its ligand PDGF are involved in various immunoregulatory processes but their role in IBD remains mostly unclear. This project aims at a detailled analysis of PDGFR expressing cell types in intestinal inflammation. Important candidates are macrophages, epithelial cells and CD4+ -T-Zellen. We are employing conditional knockout mice in different models of intestinal inflammation as well as pathogen induced inflammation. Models will include DSS colitis, T cell transfer colitis as well as C. rodentium infection. The focus of the analyses will be the defintion of the function and regulation of the innate and adaptive immune response as well as the microbiota in cell specific loss of PDGFR-alpha. Finally, implications for therapeutic options in IBD will be attained. Our preliminary data are indicating a protective role for PDGFR-alpha in intestinal macrophages. Interestingly, loss of PDGFR-alpha in macrophages leads to aggravated intestinal inflammation in DSS colitis, in part conveyed to cohoused animals by a potentially pathogenic microbiota.

• DFG Programme: Research Grants