CD1d-Restricted Antigen Presentation to Natural Killer T Cells in Intestinal Homeostasis

Natural Killer T (NKT) cells are a subset of lipid-reactive T lymphocytes, which have been shown to play a role in inflammatory bowel disease. Lipid antigens are presented by the atypical MHC class I like molecule CD1d, which is expressed by a variety of cells, including professionel antigen presenting cells, as well as intestinal epithelial cells. Here, we analyzed how antigen presentation to NKT cells mediated by intestinal epithelial CD1d affects intestinal homeostasis, as compared to antigen presentation mediated by professional antigen presenting cells. We found, that engagement of intestinal epithelial CD1d by NKT cells induces a protective feedback loop involving CD1d, HSP110, IL-10 and STAT3. Additionally, a system of proteolytically cleavable engineered CD1d molecules, which can be used for the purification of lipids bound to CD1d in vitro and in vivo is presented. This system of cleavable CD1d molecules will provide crucial information about the CD1d-associated lipid repertoire and will help in our understanding of the underlying caused of inflammatory bowel disease.


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