biased towards TH2 cells, unlike humans [61], and the functions of CRTH2 may differ between mice and humans. Indeed, IL-4 and IFN-γ production was not affected in CRTH2-deficient mice. These results do sug- gest that the cytokines and chemokines regulated by CRTH2 differ between mice and humans. Furthermore, Chevalier et al. [62] found that CRTH2-deficient mice show enhanced eosinophil recruitment into the lung, compared with their wild-type littermates, and showed that CRTH2-deficient T cells produced significantly higher amounts of IL-5 and IL-3 in vitro. These results suggest a non-redundant role for CRTH2 in restricting eosinophilia and allergic responses in vivo. The authors suggested that one possible explanation for their findings was that CRTH2 promoted IL-5 production early on, and that the inhibitory pathway was subsequently turned on. In con- trast, Satoh et al. [63] reported that allergic skin inflam- mation and IgE production were significantly diminished in CRTH2-deficient mice, consistent with the results of the pharmacological studies with human cells discussed Arima M and Fukuda T. Role of prostaglandin D2 in asthma 13 above. Studies of allergic responses in mice in which CRTH2 has been genetically deleted have so far produced conflicting results. The CRTH2-mediated effects of PGD2 may interact in a complex fashion, with redundant roles and non-redundant roles, in stimulating cytokine produc- tion and allergic inflammation. These findings suggest that CRTH2 might be a highly promising therapeutic tar- get, because CRTH2 blockade by small-molecule antago- nists is likely to attenuate TH2 activity with respect to accumulation at sites of inflammation, cytokine release, and survival in tissue (Fig. 2). Role of PGD2 in nonhematopoietic-cell functions Although minimal expression of DP was detected in the lungs of non-immunized mice, an airway OVA challenge markedly enhanced DP receptor expression [30]. Immunoelectron microscopy, using an antibody to mouse DP, revealed that the DP receptor is highly expressed on ciliated and non-ciliated epithelial cells of the bronchioles Figure 2. Hypothetical mechanism for developing asthmatic airway inflammation promoted by prostaglandin D2 (PGD2). PGD2 has been recognized as an important mediator of asthmatic airway inflammation. Critical effects of receptors, in particular the D- prostanoid receptor (DP) and chemoattractant receptor homologous molecule expressed on TH2 cells (CRTH2), are immune and inflammatory regulators of various immune cells, particularly T cells, basophil, eosinophils, mast cells, dendritic cells, and bronchial epithelial cells. CRTH2 signaling is involved in accelerating allergic inflammation by promoting chemotaxis and upregulating cytokine production. In contrast, the effect of DP signaling is mainly as an immune suppressor. MDC, macrophage-derived chemokine; TSLP, thymic stromal lymphopoietin; IL, interleukin.