Basic research about allergic rhinitis with CpG-DNA

CpG-DNA 过敏性鼻炎基础研究

基本信息

批准号：
22791581
负责人：
KUBO Seita
金额：
$ 2.5万
依托单位：
University of Fukui
依托单位国家：
日本
项目类别：
Grant-in-Aid for Young Scientists (B)
财政年份：
2010
资助国家：
日本
起止时间：
2010 至 2011
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22791581/
关键词：
CpG B細胞 PD-L1 T細胞共刺激分子 B7RP-1 CD30 アレルギー性鼻炎

项目摘要

Co-stimulatory molecules are important for regulating T cell activation and immune response. PD-L1 has emerged as an important immune modulator that can block T cell receptor signaling. We have investigated whether PD-L1 could be expressed in human B cells stimulated by CpG-DNA. CpG-DNA strongly induced the coinhibitory molecule ligand, PD-L1 of human B cells. Results show that nuclear factor-kappa B(NF-kB) signaling is involved directly in CpG-DNA-induced PD-L1 expression in human B cells. We sought to determine the effect of CpG-DNA-treated B cells on Th2 cytokine production in Cry j 1(Japanese pollen antigen)-stimulated human CD4-positive cells from patients with seasonal allergic rhinitis caused by Japanese cedar pollen. CpG-DNA-treated B cells reduced Cry j 1-induced IL-5 and IL-13 production in CD4-positive cells. When the binding of PD-1 to PD-L1 was inhibited by PD-1-Ig, this chimera-molecule reversed the previously described reductions in IL-5 and IL-13 production. These results indicate that CpG-DNA induces the coinhibitory molecule ligand PD-L1 expression in human B cells and PD-L1 can suppress Th2 cytokine production in Cry j 1-stimulated CD4-positive cells, while CpG-DNA increased Th1 cytokine production and reduced the expression of costimulatory molecule ligands that can promote Th2 inflammatory responses.

共刺激分子对于调节T细胞激活和免疫反应很重要。 PD-L1已成为可以阻止T细胞受体信号传导的重要免疫调节剂。我们已经研究了PD-L1是否可以在CpG-DNA刺激的人B细胞中表达。 CpG-DNA强烈诱导人B细胞的共抑制分子配体PD-L1。结果表明，核因子-KAPPA B（NF-KB）信号直接参与了人类B细胞中CpG-DNA诱导的PD-L1表达。我们试图确定经CPG-DNA处理的B细胞对CRY J 1（日本花粉抗原）刺激的人CD4阳性细胞中Th2细胞因子产生的影响，这些细胞来自日本雪松花粉引起的季节性过敏性鼻炎的患者。 CpG-DNA处理的B细胞在CD4阳性细胞中降低了CRY J 1-诱导的IL-5和IL-13的产生。当PD-1与PD-L1的结合被PD-1-Ig抑制时，该嵌合体分子逆转了先前描述的IL-5和IL-13产生中的降低。 These results indicate that CpG-DNA induces the coinhibitory molecule ligand PD-L1 expression in human B cells and PD-L1 can suppress Th2 cytokine production in Cry j 1-stimulated CD4-positive cells, while CpG-DNA increased Th1 cytokine production and reduced the expression of costimulatory molecule ligands that can promote Th2 inflammatory responses.