The prostaglandin D2 receptor CRTH2 is important for allergic skin inflammation after epicutaneous antigen challenge

BackgroundCutaneous prostaglandin (PG) D2 levels increase after scratching. Chemoattractant receptor–homologous molecule expressed on receptor on TH2 cells (CRTH2) mediates chemotaxis to PGD2 and is expressed on TH2 cells and eosinophils, which infiltrate skin lesions in patients with atopic dermatitis.ObjectiveWe sought to examine the role of CRTH2 in a murine model of atopic dermatitis.MethodsCRTH2−/− mice and wild-type control animals were epicutaneously sensitized by means of repeated application of ovalbumin (OVA) to tape-stripped skin for 7 weeks and then challenged by means of OVA application to tape-stripped previously unsensitized skin for 1 week. Skin histology was assessed by means of hematoxylin and eosin staining and immunohistochemistry. Cytokine mRNA expression was examined by means of quantitative RT-PCR. Levels of PGD2, antibody, and cytokines were measured by means of ELISA.ResultsPGD2 levels significantly increased in skin 24 hours after tape stripping, although not in skin subjected to repeated sensitization with OVA. Allergic skin inflammation developed normally at sites of chronic epicutaneous sensitization with OVA in CRTH2−/− mice but was severely impaired in previously unsensitized skin challenged with OVA, as evidenced by significantly decreased skin infiltration with eosinophils and CD4+ cells and impaired TH2 cytokine mRNA expression. Impaired skin inflammation at sites of acute OVA challenge in CRTH2−/− mice was not due to an impaired systemic response to epicutaneous sensitization because OVA-specific IgG1 and IgE antibody levels and OVA-driven splenocyte secretion of cytokines in these mice were comparable with those seen in wild-type control animals.ConclusionsCRTH2 promotes allergic skin inflammation in response to cutaneous exposure to antigen in previously sensitized mice.