D3.333 - Unveiling the Role of PGD2/CRTH2 Signaling in Antigen-Specific IgE Production

Previous studies demonstrated that prostaglandin D₂ (PGD₂) enhances allergic reactions to bee venom. However, the specific mechanisms by which PGD₂ exerts its effects, particularly through its receptor, the chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2), remain unclear. This study aimed to elucidate the role of PGD₂/CRTH2 signaling in allergic reactions, focusing on antigen-specific IgE production.

Wild-type (WT) and CRTH2-deficient (Crth2^⁻/⁻) mice were sensitized intradermally with ovalbumin (OVA). 

Serum levels of OVA-specific IgE and the severity of allergic reactions to OVA stimulation were significantly lower in Crth2^⁻/⁻ mice compared to WT. Immunostaining revealed that PGD₂ synthase was expressed in dendritic cells (DCs) in the lymph nodes. Furthermore, bone marrow-derived DCs released PGD₂ in response to OVA stimulation in vitro. To investigate the mechanism underlying IgE production, we examined immune cell numbers and Th2 cytokine production. In OVA-sensitized lymphatic tissues, Crth2^⁻/⁻ mice exhibited reduced immune cell numbers and lower Th2 cytokine production compared to WT mice. To identify the critical site of CRTH2 expression in allergic reactions, we transplanted WT-derived DCs into Crth2^⁻/⁻ mice. This procedure restored OVA-specific IgE production and allergic reactions, whereas transplantation of WT-derived T or B cells did not.

Our findings suggest that antigen exposure induces PGD₂ production by DCs, which enhances Th2 cytokine production in the lymph nodes through CRTH2 signaling. This pathway ultimately promotes antigen-specific IgE production, highlighting the pivotal role of PGD₂/CRTH2 signaling in allergic reactions.