【Background & Aim】 Antigen specific IgE is a fundamental factor in allergic reaction. In allergic reaction, prostaglandin D₂ (PGD₂) is known to play crucial role. PGD₂ acts on (chemoattractant receptor-homologous molecule on Th2 cells) CRTH2 receptor and its signaling is known to exacerbate allergic reaction by promoting antigen specific IgE production. However, it still be unknown the roles of PGD₂/CTH2 signaling in the production of antigen specific IgE. We aimed to reveal the role of PGD₂/CRTH2 signaling in allergic reaction.
【Methods & Results】 We sensitized wild type (WT) and CRTH2 deficient mice (Crth2^-/-) with ovalbumin (OVA) intradermally. The titer of OVA specific IgE in serum was lower in Crth2^-/- than WT after the sensitization. In the draining lymph node (dLN), the percentage of T follicular helper (Tfh) cells, a critical regulator of IgE production, was lower in Crth2^-/- than WT. These results suggested that CRTH2 signaling promotes differentiation of Tfh cells and IgE production in dLN. Intradermal administration of OVA increased the concentration of PGD₂ in the LN of WT. Immunostaining showed that the synthase of PGD₂, hematopoietic prostaglandin D synthase (HPGDS), was expressed in dendritic cells (DCs) in LN. Bone marrow derived dendritic cells released PGD₂ in response to OVA stimulation. These results suggested that antigen stimulation increased PGD₂ production in the DCs in dLN.
【Conclusion】 We found that PGD₂ derived from DC promotes antigen specific IgE production through CRTH2 signaling mediated Tfh differentiation in LN.