PGD2/CRTH2 signaling promotes acquired immunity against bee venom by enhancing IgE production.
Misato Kida, Tatsuro Nakamura, Yuki Fujiwara, Takahisa Murata
IgE‐dependent/independent activation of mast cell (MC) has been assumed to play a host defensive role against venom injection in skin. However, its detailed mechanisms remain unknown. We aimed to investigate the contribution of MC‐derived prostaglandin D2 (PGD2)‐mediated signaling in host defense against bee venom (BV). To achieve this, we utilized gene‐deficient mice of a PGD2 receptor, chemoattractant receptor‐homologous molecule expressed on Th2 cells (CRTH2). We first confirmed that subcutaneous injection of BV produced PGD2 equally in wild‐type (WT) and CRTH2‐deficient (Crth2-/-) mice skins. The BV injection dropped body temperature and impaired kidney equally in both lines of mice. In WT mice, pre‐injection of BV (3 weeks) significantly inhibited the hypothermia and kidney impairment caused by second BV injection. In contrast, this pre‐injection was not effective for the second BV injection in Crth2-/- mice. We also found that BV injections increased serum BV‐specific IgE levels in WT mice, and its serum transfused mice improved the BV‐induced hypothermia in naïve WT mice. In contrast, serum BV‐specific IgE level was significantly lower in Crth2-/- mice. FACS analysis showed the BV injection stimulate migration of dendritic cells (DCs) into regional lymph nodes in WT mice. In Crth2-/- mice, its number was significantly smaller than that of WT mice. In conclusion, PGD2/CRTH2 signaling plays defensive role against second BV injection. This signaling promotes BV‐specific IgE production at least partially by promoting DCs migration into regional lymph node.
- : The FASEB Journal
- : 10.1096/fj.202002748RR
- : http://dx.doi.org/10.1096/fj.202002748RR