During the last year, the project has focused on characterizing relationships between chemokine receptor expression and the functions of the subsets of helper T cells (CD4+ T cells) that express the receptors, in order to understand how the patterns of cell migration controlled through these receptors are integrated into the cells roles in immune and inflammatory responses. We have analyzed cells from peripheral blood of healthy donors and from cord blood using flow cytometry and cell sorting together with a variety of in vitro cellular and molecular assays to characterize the function of subsets of CD4+ T cells based on their chemokine receptor expression. We have also studied human tissue using immunohistochemistry. A principal accomplishment has been in the characterization of CD4+ T cells that can produce and secrete the proteins IL-17 and IL-22. These cells are now known as Th17 cells, a newly recognized lineage of activated and differentiated cells. Th17 cells have been implicated as critical cells in both host defense against some bacteria and in mediating tissue injury in a range of autoimmune diseases, such as Crohns disease, rheumatoid arthritis, and multiple sclerosis. We have found that all human Th17 cells express CCR6, which is the receptor for the chemokine CCL20. We hypothesize that blocking CCR6 might prevent trafficking of Th17 cells into tissue, and might, therefore, be effective therapy in treating autoimmune diseases.
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