Augmentation of antigen-presenting and Th1-promoting functions of dendritic cells by WSX-1(IL-27R) deficiency
Augmentation of antigen-presenting and Th1-promoting functions of dendritic cells by WSX-1(IL-27R) deficiency
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DOI：
10.4049/jimmunol.179.10.6421
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发表时间：
2007-11-15
影响因子：
4.4
通讯作者：
Yoshida, Hiroki
中科院分区：
文献类型：
--
作者：
Wang, Sen;Miyazaki, Yoshiyuki;Yoshida, Hiroki
WSX-1是由T、B、NK/NKT细胞以及巨噬细胞和树突状细胞（DC）表达的IL-27 R复合物的α亚基。虽然已经显示IL-27对T细胞具有刺激和抑制作用，但是关于IL-27[WSX-1]对DC的作用知之甚少。LPS刺激体内脾DC导致WSX-1缺陷型DC上的CD 80/CD 86表达比野生型D延长。在体外LPS刺激后，WSX-1缺陷型DC表达的Th 1促进分子高于野生型DC。在同种异体MLR试验中，WSX-1缺陷型DC在诱导应答细胞增殖和IFN-γ产生方面比野生型DC更有效。当与纯化的NK细胞共培养时，WSX-1缺陷型DC诱导更高的IFN-γ产生和NK细胞的杀伤活性比野生型DC高。因此，Ag脉冲的WSX-1缺陷型DC在体内转移时诱导Th 1偏向的强免疫应答超过野生型DC。WSX-1缺陷型DC与野生型DC相比，通过细胞因子的产生对LPS刺激具有高反应性。IL-27在体外抑制LPS诱导的DC的CD 80/86表达和细胞因子产生。因此，我们的研究表明，IL-27/WSX-1信号转导有力地下调APC功能和Th 1促进功能的DC调节整体免疫应答。
WSX-1 is the a subunit of the IL-27R complex expressed by T, B, NK/NKT cells, as well as macrophages and dendritic cells (DCs). Although it has been shown that IL-27 has both stimulatory and inhibitory effects on T cells, little is known on the role of IL-27[WSX-1 on DCs. LPS stimulation of splenic DCs in vivo resulted in prolonged CD80/CD86 expression on WSX-1-deficient DCs over wild-type D(is. Upon LPS stimulation in vitro, WSX-1-deficient DCs expressed Th1-promoting molecules higher than wild-type DCs. In an allogeneic MLR assay, WSX-1-deficient DCs were more potent than wild-type DCs in the induction of proliferation of and IFN-gamma production by responder cell proliferation. When cocultured with purified NK cells, WSX-1-deficient DCs induced higher IFN-gamma production and killing activity of NK cells than wild-type DCs. As such, Ag-pulsed WSX-1-deficient DCs induced Th1-biased strong immune responses over wild-type DCs when transferred in vivo. WSX-1-deficient DCs were hyperreactive to LPS stimulation as compared with wild-type DCs by cytokine production. IL-27 suppressed LPS-induced CD80/86 expression and cytokine production by DCs in vitro. Thus, our study demonstrated that IL-27/WSX-1 signaling potently down-regulates APC function and Th1-promoting function of DCs to modulate overall immune responses.