Paradoxical increase in skin inflammation in the absence of CCR4

The chemokine receptors are seven transmembrane, G-protein-coupled surface receptors that play key roles in the migration and localization of leukocytes to the skin during physiologic and inflammatory states. Their ligands, chemokines, are small secreted proteins that initiate leukocyte chemoattraction. Recent data indicate that known subsets of T helper (Th) cells express signature chemokine receptors (e.g., CXCR3, CCR3/4, and CCR6) that help to define individual subsets such as Th1, Th2, and Th17 cells, respectively, although there is some degree of overlap among these T-cell subsets. In this issue, Lehtimäki et al. use an oxazolone-induced contact hypersensitivity (CHS) model to show that T cells (as well as neutrophils and eosinophils) from CCR4(-/-) mice accumulate just as (if not more) efficiently in inflamed skin as compared with the same population of leukocytes from wild-type (WT) mice. Although somewhat unexpected, their results can be explained if CCR4 attracts both proinflammatory and suppressive T cells into skin in addition to serving functions that are partially redundant with those of CCR10. Finally, we discuss other possible roles for CCR4 in the homing of T cells to skin.