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The role of IRF transcription factors between the differentiation of T cells and dendritic cells

Laufzeit: 01.01.2008 - 31.12.2009

Kurzfassung

Gut specimen of at least 100 IBD patients and 100 control patients will be collected and evaluated for IRF-4 expression and for the expression of other IRFs (e.g. IRF-3, IRF-7). The correlation between the degree of inflammation, the disease localization, the disease phenotype and IRF-4 expression in Crohns disease and ulcerative colitis will be analyzed. The type of IRF-4 expressing cells will be also evaluated: T cells might play a predominant role, but also DCs must be considered. We...Gut specimen of at least 100 IBD patients and 100 control patients will be collected and evaluated for IRF-4 expression and for the expression of other IRFs (e.g. IRF-3, IRF-7). The correlation between the degree of inflammation, the disease localization, the disease phenotype and IRF-4 expression in Crohns disease and ulcerative colitis will be analyzed. The type of IRF-4 expressing cells will be also evaluated: T cells might play a predominant role, but also DCs must be considered. We will detect areas in the lamina propria with high invasion of bacteria (via confocal endoscopic imaging in vivo) and take biopsies in these areas to detect dendritic cells. Double staining of IRF-4 and DCs will serve to study the potential correlation between bacterial invasion of the lamina propria and IRF-4 expression in dendritic cells. Due to the fact that the expression of IL-6 is decreased in experimental colitis in IRF-4 deficient mice at the transcriptional level, IL-6 promoter studies in human DCs and T cells will give information about human IRF-4/IL-6 promoter interaction. Additionally in vitro co-transfection of IRF-4 and IL-6 promoter constructs will complete the experimental setting. Importantly, we will also screen samples from IBD patients for other IRF transcription factors and cell types that express IRFs. This might be important to identify candidate transcription factors of the IRF family that play a key regulatory role in IBD. Furthermore, these studies may help to design markers for prognosis of IBD patients and to delineate novel target structures for therapy. » weiterlesen» einklappen