CCR6-deficient mice have impaired leukocyte homeostasis and altered contact hypersensitivity and delayed-type hypersensitivity responses

CCR6 expression in dendritic, T, and B cells suggests that this beta -chemo kine receptor may regulate the migration and recruitment of antigen-present ing and immunocompetent cells during inflammatory and immunological respons es. Here we demonstrate that CCR6(-/-) mice have underdeveloped Peyer's pat ches, in which the myeloid CD11b(+) CD11c(+) dendritic-cell subset is not p resent in the subepithelial dome. CCR6(-/-) mice also have increased number s in T-cell subpopulations within the intestinal mucosa. In 2,4-dinitrofluo robenzene-induced contact hypersensitivity (CHS) studies, CCR6(-/-) mice de veloped more severe and more persistent inflammation than wild-type (WT) an imals. Conversely, in a delayed-type hypersensitivity (DTH) model induced w ith allogeneic splenocytes, CCR6(-/-) mice developed no inflammatory respon se. The altered responses seen in the CHS and DTH assays suggest the existe nce of a defect in the activation and/or migration of the CD4(+) T-cell sub sets that downregulate or elicit the inflammation response, respectively. T hese findings underscore the role of CCR6 in cutaneous and intestinal immun ity and the utility of CCR6(-/-) mice as a model to study pathologies in th ese tissues.