The purpose of the project is to investigate the biological roles of members of the chemokine family of cytokines by studying the actions of chemokines and their receptors in vivo, particularly in mouse models of infectious and inflammatory/autoimmune disease. Chemokines and their receptors are critical for leukocyte trafficking, and our experiments are directed to understanding how manipulating the chemokine system could be used to treat diseases in which leukocytes play a critical role. In the last year, we have focused on a mouse model of skin inflammation that has features of psoriasis. The model involves injection of a cytokine, IL-23, which appears to have a role not only in psoriasis, but also in other immune-mediated diseases, such as Crohns disease. We and others had described that the chemokine receptor CCR6 is expressed on a newly recognized type of helper T lymphocyte, Th17 cells, that depend on IL-23 and that are thought to be important in causing tissue injury in autoimmune diseases. Using mice that we had produced that lack the CCR6 (CCR6 knockout mice), we discovered that CCR6 was essential for the psoriasis-like changes induced by injecting IL-23. These data suggest that CCR6 should be investigated as a potential drug target in psoriasis and other inflammatory diseases in which IL-23 plays a role.

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