Protective function of PDGFR-alpha in intestinal Inflammation

该项目的目标是确定PDGFR-α在肠道炎症中的作用，从而深入了解炎症性肠病（IBD）的病理机制。PDGFR及其配体PDGF参与各种免疫调节过程，但它们在IBD中的作用大多仍不清楚。本项目旨在详细分析肠道炎症中表达PDGFR的细胞类型。重要的候选者是巨噬细胞、上皮细胞和CD 4 + -T-Zellen。我们在不同的肠道炎症模型以及病原体诱导的炎症中使用条件性基因敲除小鼠。模型将包括DSS结肠炎、T细胞转移结肠炎以及C.啮齿类感染分析的重点将是先天性和适应性免疫应答的功能和调节以及PDGFR-α细胞特异性损失中的微生物群的定义。最后，将获得IBD治疗选择的影响。我们的初步数据表明PDGFR-α在肠道巨噬细胞中具有保护作用。有趣的是，巨噬细胞中PDGFR-α的丢失导致DSS结肠炎的肠道炎症加重，部分通过潜在的致病性微生物群传递给共同饲养的动物。

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.