Regulation of Immune Response by histamine receptor-mediated signal.

在本项目中，我们阐明了组胺受体介导的信号在获得性免疫反应调节中的意义。由于组胺是由肥大细胞、巨噬细胞和各种炎症细胞产生的，这是先天免疫对获得性免疫调节机制的又一例证。1)我们发现Th1辅助T细胞优先表达组胺H1受体(H1R)，而Th2细胞优先表达H2受体(H2 R)。来自H1R的信号强烈上调Th1反应，导致干扰素_γ的产生增加。另一方面，组胺通过过氧化氢受体下调Th2反应。随后，组胺引发作用于血管内皮细胞和血管平滑肌的过敏反应，通过诱导Th1优势来下调IgE反应。因此，组胺本身作为一种反馈机制停止了过敏反应。Th1细胞上的H1R信号促进干扰素_γ的产生，因此它似乎与Th1型自身免疫性疾病的恶化有关。另一方面，我们的结果清楚地表明，组胺通过过氧化氢受体强烈下调肝脏的炎症反应。我们的结果有力地表明，组胺在2型受体中起着至关重要的作用。

In the present project, we have clarified a significance of histamine receptor-mediated signals on the regulation of acquired immune response. Since histamine is produced by mast cells, macrophages and various inflammatory cells, this is another example of regulatory mechanism of innate immunity to the acquired immunity. 1)we have shown that Th1 helper T cells preferentially express histamine H1 receptors(H1R), while Th2 cells express preferentially H2 receptors(H2R). Signals from H1R strongly up-regulates Th1 response leading to enhanced production of IFN_γ. On the other hand, histamine down-regulates Th2 responses via H2R. Subsequently, histamine, which triggers allergic reaction acting on endothelial cells, smooth muscles of blood vessels, down regulates IgE response by induction of Th1 dominance. Thus, histamine itself ceases allergic reaction as a feedback mechanism. Signals from H1R on Th1 cells enhances IFN_γ production, thus it appears to be involved in deterioration of Th1 type autoimmune diseases. On the other hand, our results clearly demonstrated that histamine strongly down regulated inflammatory responses in liver via H2R. Our results strongly indicate that histamine plays a crucial role inne receptor type 2.