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Publication : PGD<sub>2</sub> /CRTH2 signaling promotes acquired immunity against bee venom by enhancing IgE production.

First Author  Kida M Year  2021
Journal  FASEB J Volume  35
Issue  6 Pages  e21616
PubMed ID  33978990 Mgi Jnum  J:309144
Mgi Id  MGI:6756302 Doi  10.1096/fj.202002748RR
Citation  Kida M, et al. (2021) PGD2 /CRTH2 signaling promotes acquired immunity against bee venom by enhancing IgE production. FASEB J 35(6):e21616
abstractText  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 naive 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.
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