Critical role for CXC chemokine ligand 16 (SR-PSOX) in Th1 response mediated by NKT cells
Critical role for CXC chemokine ligand 16 (SR-PSOX) in Th1 response mediated by NKT cells
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DOI：
10.4049/jimmunol.179.12.8172
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发表时间：
2007-12-15
影响因子：
4.4
通讯作者：
Yonehara, Shin
中科院分区：
文献类型：
--
作者：
Shimaoka, Takeshi;Seino, Ken-ichiro;Yonehara, Shin
跨膜趋化因子CXCL 16（CXCL 16）是与结合磷脂酰丝氨酸和氧化脂蛋白的清道夫受体（SR-PSOX）相同的分子，已显示其介导表达CXC趋化因子受体6的细胞如NKT和活化的Th 1细胞的趋化性和粘附。我们产生了SR-PSOX/CXCL 16缺陷小鼠，并检查了这种趋化因子在体内的作用。突变小鼠显示出肝脏NKT细胞数量减少，并且通过施用α-半乳糖神经酰胺（α GalCer）减少IFN-γ和IL-4的产生。值得注意的是，在SR-PSOX缺陷小鼠中，α GalCer诱导的IFN-γ产生比IL-4产生更严重受损。在这种情况下，SR-PSOX缺陷小鼠显示出对aGalCer诱导的由来自NKT细胞的IFN-γ介导的抗肿瘤作用的敏感性受损。来自野生型小鼠的NKT细胞在与来自突变型小鼠的α GalCer和APC培养后显示IFN-γ的产生受损，但不显示IL-4。此外，痤疮丙酸杆菌诱导的体内Th 1应答在SR-PSOX缺陷以及NKT KO小鼠中严重受损。总之，SR-PSOX/CXCL 16不仅在NKT细胞产生IFN-γ中起重要作用，而且在促进NKT细胞介导的Th 1倾向的免疫应答中起重要作用。
The transmembrane chemokine CXCL 16 (CXCL16), which is the same molecule as the scavenger receptor that binds phosphatidylserine and oxidized lipoprotein (SR-PSOX), has been shown to mediate chemotaxis and adhesion of CXC chemokine receptor 6-expressing cells such as NKT and activated Th1 cells. We generated SR-PSOX/CXCL16-deficient mice and examined the role of this chemokine in vivo. The mutant mice showed a reduced number of liver NKT cells, and decreased production of IFN-gamma and IL-4 by administration of alpha-galactosylceramide (alpha GalCer). Of noted the alpha GalCer-induced production of IFN-gamma was more severely impaired than the production of IL-4 in SR-PSOX-deficient mice. In this context, SR-PSOX-deficient mice showed impaired sensitivity to aGalCer-induced anti-tumor effect mediated by IFN-gamma from NKT cells. NKT cells from wild-type mice showed impaired production of IFN-gamma, but not IL-4, after their culture with alpha GalCer and APCs from mutant mice. Moreover, Propionibacterium acnes-induced in vivo Th1 responses were severely impaired in SR-PSOX-deficient as well as NKT KO mice. Taken together, SR-PSOX/CXCL16 plays an important role in not only the production of IFN-gamma by NKT cells, but also promotion of Th1-inclined immune responses mediated by NKT cells.