期刊
FASEB JOURNAL
卷 35, 期 6, 页码 -出版社
WILEY
DOI: 10.1096/fj.202002748RR
关键词
biological defense; IgE production; lipid mediator
资金
- MEXT | Japan Society for the Promotion of Science (JSPS) [18K14603, 20H05678]
- Shimadzu Science Foundation
- Kobayashi Foundation
- Takeda Science Foundation
- Grants-in-Aid for Scientific Research [20H05678, 18K14603] Funding Source: KAKEN
The study revealed that the PGD(2)/CRTH2 signaling pathway plays a defensive role in host response to bee venom injection, promoting the production of BV-specific IgE and facilitating the migration of DCs to regional lymph nodes.
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 D-2 (PGD(2))-mediated signaling in host defense against bee venom (BV). To achieve this, we utilized gene-deficient mice of a PGD(2) receptor, chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2). We first confirmed that subcutaneous injection of BV produced PGD(2) 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, PGD(2)/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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