Prostaglandin D2 (
PGD2) is a
prostanoid implicated in allergic
inflammation. However, the roles of
PGD2 in immune and allergic responses remain controversial.
PGD2 exerts its effect through the CRTH2 and DP receptors. To elucidate functional differences of
PGD2 and its receptors in chronic skin
inflammation, chronic
contact hypersensitivity (chronic CHS) and
IgE-mediated chronic allergic skin
inflammation (
IgE-CAI) were induced in mice deficient in the CRTH2 and/or DP genes. DP (-/-) mice and CRTH2 (-/-)/DP (-/-) mice showed exacerbated chronic CHS, and conversely, CRTH2 (-/-) mice exhibited diminished skin responses. Skin responses correlated with local levels of
IL-13, CCL11, and CCL22. These phenotypic changes in chronic CHS of mutant mice were similar to those in acute CHS despite the differences in the
cytokine milieus; chronic CHS and acute CHS were mediated by Th2 and Th1/Th17 immunity, respectively. However, in
IgE-CAI, DP (-/-) mice showed comparable skin responses to wild-type mice. Alleviation of
IgE-CAI was observed in CRTH2 (-/-) mice, and as a consequence, CRTH2 (-/-)/DP (-/-) mice exhibited diminished
IgE-CAI compared with wild-type mice.
IgE-CAI in mutant mice correlated with local
IL-4 and CCL22 production. Consistent with these results, a CRTH2-specific antagonist exerted inhibitory effects in both chronic CHS and
IgE-CAI. The present study demonstrates that functional roles of
PGD2 and its receptors appear to depend on the nature of the
inflammation. Nevertheless, tools targeted against PGD2-CRTH2 signals could offer therapeutic potential for both types of chronic skin
inflammation.