Control of intestinal inflammation by the D6 decoy chemokine receptor

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Chemokines are small chemical messengers which play an important role in inflammation and are involved in the diseases caused by excessive or inappropriate inflammation. The body has to control the levels and functions of these important messengers. One way this can be done is by the use of specialised molecules that bind chemokines and destroy them. We have discovered one of these molecules, known as D6, that removes inflammatory chemokines. However, surprisingly, our recent work suggests that D6 may actually have a positive role in intestinal inflammation rather than preventing it. This is associated with increased production of another important chemical messenger of the immune system, interleukin 17. The purpose of this application is to investigate how D6 can control colitis, by finding which cells it is present on in the colon and by examining how D6 controls interleukin 17 in the intestine. We will look at specialised cells known as dendritic cells (DC) which are known to stimulate other cells to make interleukin 17 preferentially. By understanding the links between these different chemical messengers in the intestine, we hope ultimately to assist the development of new treatments for inflammatory diseases