Inflammatory Bowel Disease

Inflammatory bowel disease  ( Back to main page)
Inflammatory bowel disease (IBD) is a chronic disease of the intestinal tract caused by aberrant inflammatory immune responses to harmless microbiota. Two clinical subtypes of disease Crohn's disease (CD) and Ulcerative colitis are distinguished. Both innate and adaptive immune responses contribute to the disease pathogenesis. However, excessive responses by inflammatory T-cells secreting interferon-? (IFN-?) or interleukin-17 (IL-17) drive the chronicity of IBD. Currently, patients are invariably treated with immune suppressants. Unfortunately, in approximately 30% of patients this therapy is insufficient entailing a risk of operation to remove the chronically inflamed intestinal segments.


In our translational work we have focused on dissecting inflammatory pathways that classify IBD patients in subgroups and yield parameters to characterize their disease subtype and therapy responsiveness. Since 2009 we have started our longitudinal IBD study for which we are collecting patient peripheral blood, biopsies and buccal epithelium at diagnosis and fixed intervals during treatment. Using our newly acquired fundamental mucosal immunology knowledge phenotypic markers are designed to classify disease subtypes.


For example in our mouse systems we have identified that the mucosal factors TGF- ? and retinoic acid induced a very selective expression pattern on differentiating CD4 + T cells in the mesenteric lymph node (4). This TGF- ? - and retinoic acid- induced surface expression of CD62LnegCD38+ was also found to occur on human cells. In consequence we investigated whether the CD62LnegCD38+ phenotype could be used as a marker to identify circulating mucosal T cells in peripheral blood. In a collaborative study we established that indeed the CD62LnegCD38 + phenotype very selectively identifies gluten-specific circulating T cells in peripheral blood of bread challenged Celiac Disease patients. The value of defining this new subset lies in lowering the threshold for detection of luminal antigen specific T cells within the circulating CD4+ T-cell pool. This is of pivotal importance for functional studies as this method removes 90-95% of CD4+ non-gut imprinted effector T cells and naive T cells from the analysis. Current studies aim at characterizing circulating mucosal T cells from IBD patients and identifying their microbial specificity which is expected to be pivotal for identifying disease subtypes.


More recently, our translational work has expanded to studying IBD that arises in infants with genetic defects amongst which the IL-10R deficiency. Thorough analysis of these infants reveals pathways that are pivotal for intestinal tolerance in human and uncover patterns of inflammation that evolve from a particular defect. In turn, these patterns can be used to identify whether similar disease subtypes can be found in adolescent IBD and stem from a similar immune dysfunction.


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