Role of G protein coupled receptor (GPCR)-mediated signals in the activation of immune cell.

据报道，T细胞和B细胞在其细胞表面表达各种G蛋白偶联受体(GPCR)。在本研究中，我们研究了GPCR介导的信号在抗原刺激下T细胞和B细胞中抗原受体介导的信号转导中的作用。目前的研究阐明了GPCR介导的信号和抗原受体介导的信号转导之间存在密切的相互作用。GPCRGaq与组胺H1受体(H1R)偶联，Gas与组胺H2 R结合。成熟的T和B细胞同时表达H1R和H2 R。我们以前通过基因打靶建立了H1R和H2 R缺陷小鼠。H1R缺陷的T和B细胞对抗原刺激或抗CD3或抗IgM抗体引起的受体交联反应显著降低，提示GAQ信号(S)在抗原受体介导的信号转导中起重要作用。组胺是即刻超敏反应的主要化学介质之一。…更多的药理学研究也表明，组胺可能通过其受体的信号(S)影响Th类型的辅助T细胞。在抗原刺激下，检测了这些突变小鼠的耳部过敏反应和脾细胞产生的细胞因子。H1R基因缺陷小鼠对组胺、抗DNP-IgE和OVA引起的变态反应有明显的抑制作用。5-羟色胺增加H1R缺陷小鼠的血管通透性，但强度小于野生型小鼠。而H_2R缺乏的小鼠则表现出正常的过敏反应。干扰素γ的产生在H1R缺陷小鼠显著减少，而在H 2R缺陷小鼠增加。在H_2R缺乏的小鼠中，IL-13的产生显著增加。在H1R缺陷小鼠中也观察到了这种增强。这些结果表明，皮肤过敏反应中血管通透性的增加主要受H1R信号调节，而不受H2 R信号的调节。此外，来自H1R的信号可能在Th1激活的正向调节中起关键作用，而来自H2 R的信号可能对Th1和Th2的激活起负向调节作用。较少

It has been reported that T and B cells express various kinds of G protein coupled receptors (GPCR) on their cell surface. In the present study, we investigated the effects of GPCR-mediated signals on the antigen receptor-mediated signal transduction in T and B cells upon antigen stimulation. The present studies clarified the presence of a close cross-talk between GPCR-mediated signaling and antigen receptor-mediated signal transduction. GPCR Gaq coupled to histamine H1 receptor (H1R) and Gas associates with histamine H2R.Mature T and B cells express both H1R and H2R.We previously established H1R- and H2R-deficient mice by gene targeting. The H1R-deficient T and B cells showed a remarkably reduced responses against antigen stimulation or crosslinking of the receptor by anti-CD3 or anti-IgM antibody, indicating that signal (s) from Gaq plays a essential role in antigen receptor-mediated signal transduction. Histamine is one of major chemical mediators of immediate-type hypersensitivity. … More Pharmacological studies have been also suggested that histamine may affect Th types of helper T cells via a signal (s) from their receptors. Allergic reaction elicited in the ears as well as cytokine production from spleen cells of these mutant mice were examined upon stimulation with antigen. The allergic reactions induced by histamine, anti-DNP IgE and OVA were significantly inhibited in H1R-deficient mice. Serotonin increased vascular permeability in H1R-deficient mice, however the intensity was lesser than that of wild-type mice. Whereas H2R-deficient mice exhibited normal allergic reactions. IFNγ production was markedly reduced in H1R-deficient mice, whereas that was increased in H2R-deficient mice. IL-13 production was greatly enhanced in H2R-deficient mice. Such enhancement was also observed in H1R-deficient mice. These results suggest that increased vascular permeability in cutaneous anaphylaxis is mainly regulated by H1R signaling but not by H2R signaling. Moreover, the signal from H1R may play a crucial role in positive regulation of Th1 activation, whereas that from H2R may negatively regulate Th1 as well as Th2 activation. Less