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

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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