Chemokine receptors and leukocyte trafficking in the mucosal immune system

The CC chemokine receptors CCR6, CCR9, and CCR10 all contribute to the positioning of leukocytes at mucosal locations. Mucosal epithelial cells are major sources of the chemokine ligands for each of these receptors, although the pattern of expression of the individual ligands differs at distinct mucosal sites. CCR6 is expressed by most B cells, subsets of CD4 and CD8 memory T cells, and subsets of dendritic cells (DCs). Absence of CCR6 in mice leads to abnormal expansion of intestinal intraepithelial T cells and lamina propria T cells, smaller Peyer's patches, and defects in IgA-mediated responses to oral antigens and pathogens. CCR9 is present on thymocytes, most intestinal intraepithelial lymphocytes, and other types of intestine-homing T cells. CCR10 is found on skin-homing T cells and also directs IgA-producing plasma cells into mucosal sites. This review discusses the role of these chemokine receptors in homeostatic regulation of the mucosal immune system.