Tanaka Kazuya, Hirai Hiroyuki, Takano Shoichi, Nakamura Masataka, Nagata Kinya
Department of Advanced Medicine and Development, BML, Inc., Saitama 350-1101, Japan.
Biochem Biophys Res Commun. 2004 Apr 16;316(4):1009-14. doi: 10.1016/j.bbrc.2004.02.151.
Prostaglandin (PG) D(2) is abundantly produced by mast cells in the sites of allergic inflammations and acts on various cell types through its receptors DP and CRTH2. Among human T cells, CRTH2 is preferentially expressed on Th2-type cells. However, distribution of DP among T cells and impacts of CRTH2- and DP-mediated signals on T cell functions are presently unclear. Here, we show that CD4(+) and CD8(+) T cells producing IFN-gamma and IL-2 were reduced by DP-mediated signals, while CRTH2-mediated signals enhanced IL-2, IL-4, IL-5, and IL-13 production by Th2 cells. CRTH2 signals also caused up-regulation of CD11b and CD40L in resting Th2 cells. RT-PCR analysis revealed distribution of DP among Th cell subsets. On CRTH2(+) Th2 cells, the CRTH2-mediated PGD(2) effects were dominantly observed. Thus, PGD(2) favors Th2 functions through CRTH2 while restraining Th1 functions via DP, which may contribute to development of Th2-dominated status in allergic inflammations.
前列腺素（PG）D2在过敏性炎症部位由肥大细胞大量产生，并通过其受体DP和CRTH2作用于多种细胞类型。在人类T细胞中，CRTH2在Th2型细胞上优先表达。然而，目前尚不清楚DP在T细胞中的分布以及CRTH2和DP介导的信号对T细胞功能的影响。在此，我们表明，产生IFN-γ和IL-2的CD4(+)和CD8(+) T细胞因DP介导的信号而减少，而CRTH2介导的信号增强了Th2细胞产生IL-2、IL-4、IL-5和IL-13的能力。CRTH2信号还导致静息Th2细胞中CD11b和CD40L上调。RT-PCR分析揭示了DP在Th细胞亚群中的分布。在CRTH2(+) Th2细胞上，主要观察到CRTH2介导的PGD2效应。因此，PGD2通过CRTH2促进Th2功能，同时通过DP抑制Th1功能，这可能有助于在过敏性炎症中形成以Th2为主导的状态。
