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GRK 1482 Jahrbuch 2011-2014

Abstract Inflammatory bowel disease (IBD) is characterized by severe gastro- intestinal inflammation. Activation of innate immune responses, Th17 responses and/or deficiency of regulatory T cells are major factors that drive pathogene-sis of IBD. Western diet mostly composed of meat and other iron rich foods as well oral iron therapy were shown to correlate with inflammation in IBD patients. The mechanism that explains the influence of luminal iron on intestinal inflammation is not fully understood. We plan to elucidate the influence of luminal iron on antigen presen- tation with main focus on macrophages and DCs and their interaction with T cells in the gut. Introduction The disease process of inflammatory bowel disea- ses (IBD) is initiated and driven by the interaction of intestinal microflora and environmental factors in a genetically susceptible host [1]. Except smoking, very few studies have been pub- lished concerning environmental factors that can contribute to the pathogenesis of IBD. Since one of the most common complications of this disease is iron deficiency-anemia as a result of chronic blee- ding due to the persistent injury of colonic mucosa, IBD patients are suggested to consume diet rich in protein and iron like red meat and iron fortified foods. Moreover, patients are very often submitted to oral or parenteral iron supplementation. However, recent studies have shown that oral iron supple- mentation and iron rich foods are very often poorly tolerated in IBD patients showing enhanced in- flammation and mucosal damage most likely due to the prooxidative capacity of iron which leads to the ROS and iNOS production by activated innate immune cells in already damaged mucosa [2]. In addition, Werner et al. found that luminal iron may directly affect intestinal epithelial cell (IEC) function and generate a pathological milieu in the intestine that triggers epithelial cell stress associated apop- tosis through changes in microbial homeostasis [3]. The immunobiology of intestinal macrophages is still poorly understood due to the difficulty in iso- lating them but also in distinguishing them from other intestinal myeloid cells like DCs. There are very few studies trying to explain the possible influ- ence of iron on macrophage activation. In intestinal inflammation, a state that is found in IBD patients or animal model of colitis, enhanced inflammation due to iron overload involving macrophages activa- tion can be either a consequence of changes in intestinal milieu in terms of microbiota alterations and IEC layer destruction or can be due to direct activation of these cells. Both, CX3CR1int macro- phages/DCs and CX3CR1hi resident macrophages, which extend transepithelial dendrites (TED) into intestinal lumen may participate in the proinflamm- atory response to luminal iron [4]. Anamarija Markota (M.Sc.) Klinikum rechts der Isar | Internal Medicine II PhD 1/2 Dietary iron as environmental factor influencing antigen presentation and T-cell differentiation in inflammatory bowel diseases PhD FELLOWS Page 36 | GRK Progress Report 2011-2014