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IBDlipids Report Summary

Project ID: 336528
Funded under: FP7-IDEAS-ERC
Country: Germany

Mid-Term Report Summary - IBDLIPIDS (Lipid antigens in intestinal inflammation and tumor development)

Inflammatory bowel diseases (IBD) are a group of diseases characterized by chronic intestinal inflammation and an increased risk of colorectal cancer. While the precise mechanisms leading to IBD are not known, current immunosuppressive treatment is of limited efficacy and associated with severe side effects such as susceptibility to infection and malignancy. There is thus an unmet need for novel and more efficacious therapies. Natural killer T (NKT) cells are a subset of T cells that recognize lipid antigens presented by CD1d and that contribute to the development of intestinal inflammation in IBD. These observations suggest that interference with lipid antigen presentation and NKT cell activation might provide a novel approach for the treatment of IBD.
In this project, two main goals were defined. First, given that CD1d is widely expressed across different cell types, we aimed to address whether CD1d exerts cell-type specific roles in intestinal inflammation and to define the cellular origin of CD1d- and NKT cell-dependent intestinal inflammation. Second, we aimed to identify lipid antigens, which promote NKT cell-dependent intestinal inflammation in IBD.

In the studies completed so far, we could demonstrate that CD1d can play both protective as well as pathogenic roles in intestinal inflammation. As such, while CD1d in the intestinal epithelium, the cell layer that separates the intestinal microbiota from host tissue, elicits protective effects in intestinal inflammation, bone marrow-derived immune cells facilitate inflammation in a manner dependent on CD1d and NKT cells. These studies demonstrate that strategies for interference with lipid antigen presentation in IBD likely require cell-specific approaches for therapeutic targeting. Current work focuses on the question of whether diverse and opposing roles of CD1d in NKT cell-dependent intestinal inflammation result from the presentation of specific lipid antigens and whether such knowledge can be used to target lipid antigens in the treatment of IBD.

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