Endothelial Cell-Derived Chemerin Promotes Dendritic Cell Transmigration
Endothelial Cell-Derived Chemerin Promotes Dendritic Cell Transmigration
复制标题
DOI：
10.4049/jimmunol.1302028
复制
发表时间：
2014-03-01
影响因子：
4.4
通讯作者：
Sozzani, Silvano
中科院分区：
文献类型：
--
作者：
Gonzalvo-Feo, Safiye;Del Prete, Annalisa;Sozzani, Silvano
ChemR 23是由APC（如树突状细胞、巨噬细胞和NK细胞）表达的趋化性受体。Chemerin，ChemR 23配体，通过免疫组织化学检测，与自身免疫性疾病，如红斑狼疮，银屑病和类风湿性关节炎中的炎症内皮细胞相关。本研究报告，血液和淋巴管内皮细胞产生chemerin后视黄酸刺激。相反，促炎细胞因子，如TNF-α、IFN-γ和LPS或骨化三醇，则无效。视黄酸刺激的内皮细胞促进树突状细胞在切应力条件下的粘附和迁移的ChemR 23依赖的方式。活化的内皮细胞上调非典型趋化受体CCRL 2/ACKR 5的表达，CCRL 2/ACKR 5是一种能够结合并呈递趋化素至ChemR 23（+）树突细胞的非信号受体。因此，活化的内皮细胞在质膜上表达趋化素，并以更有效的方式促进树突状细胞的趋化素依赖性迁移。最后，chemerin刺激髓系树突状细胞诱导VCAM-1/CD 106 Fc嵌合蛋白的高亲和力结合，并促进VCAM-1依赖性阻滞在剪切应力条件下的固定化配体。总之，本研究报告，视黄酸激活的内皮细胞可以促进髓样和浆细胞样树突状细胞穿越内皮细胞单层，通过内源性产生chemerin，上调CCRL 2，和树突状细胞β（1）整合素亲和力的激活。
ChemR23 is a chemotactic receptor expressed by APCs, such as dendritic cells, macrophages, and NK cells. Chemerin, the ChemR23 ligand, was detected by immunohistochemistry, to be associated with inflamed endothelial cells in autoimmune diseases, such as lupus erythematosus, psoriasis, and rheumatoid arthritis. This study reports that blood and lymphatic murine endothelial cells produce chemerin following retinoic acid stimulation. Conversely, proinflammatory cytokines, such as TNF-alpha, IFN-gamma, and LPS, or calcitriol, are not effective. Retinoic acid-stimulated endothelial cells promoted dendritic cell adhesion under shear stress conditions and transmigration in a ChemR23-dependent manner. Activated endothelial cells upregulated the expression of the atypical chemotactic receptor CCRL2/ACKR5, a nonsignaling receptor able to bind and present chemerin to ChemR23(+) dendritic cells. Accordingly, activated endothelial cells expressed chemerin on the plasma membrane and promoted in a more efficient manner chemerin-dependent transmigration of dendritic cells. Finally, chemerin stimulation of myeloid dendritic cells induced the high-affinity binding of VCAM-1/CD106 Fc chimeric protein and promoted VCAM-1-dependent arrest to immobilized ligands under shear stress conditions. In conclusion, this study reports that retinoic acid-activated endothelial cells can promote myeloid and plasmacytoid dendritic cell transmigration across endothelial cell monolayers through the endogenous production of chemerin, the upregulation of CCRL2, and the activation of dendritic cell beta(1) integrin affinity.