【Background & Aim】 We previously showed that prostaglandin D₂ (PGD₂) promotes allergic reaction by increasing antigen-specific IgE production. In the present study, we investigated the mechanism underlying the promotion of IgE production by PGD₂focusing on the role of its receptor, chemoattractant receptor-homologous molecule on Th2 cells (CRTH2).
【Methods & Results】 We intradermally sensitized wild type (WT) and CRTH2 deficient mice (Crth2^-/-) with ovalbumin (OVA). The serum OVA specific IgE level and the allergic reaction against OVA stimulation were lower in Crth2^-/- than those of WT. Immunostaining of lymph nodes showed that dendritic cells (DCs) expressed PGD₂ synthase. Consistently, bone marrow derived DCs released PGD₂ in response to OVA stimulation in vitro. The OVA-sensitization increased immune cell number in lymph node and Th2 cytokine productions from lymphocytes in WT. CRTH2 deficiency significantly decreased the immune cell number and cytokine productions. We finally revealed that intravenous transplantation of WT DCs but not T cells or B cells restored the serum levels of OVA specific IgE production and allergic reaction in Crth2^-/-.
【Conclusion】 In summary, antigen invasion stimulates PGD₂ production from DCs which promotes Th2 cytokine production in lymph node through CRTH2 signaling. These phenomena result in promoting antigen specific IgE production.