Osteopontin promotes inflammation in patients with acute coronary syndrome through its activity on IL-17 producing cells
Osteopontin promotes inflammation in patients with acute coronary syndrome through its activity on IL-17 producing cells
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骨桥蛋白通过其对 IL-17 产生细胞的活性促进急性冠状动脉综合征患者的炎症
DOI：
10.1002/eji.201242475
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发表时间：
2012-10-01
影响因子：
5.4
通讯作者：
Xu, Dakang
中科院分区：
文献类型：
--
作者：
Zheng, Yingxia;Wang, Zhihao;Xu, Dakang
动脉粥样硬化是一种进行性疾病，具有强烈的炎症成分。在此，我们证实了急性冠脉综合征(ACS)患者外周血中Th17/Treg细胞比例存在严重失衡，这有利于炎症反应。同时，急性冠脉综合征患者外周血中CD4+CD45RA-FOXP3lo Treg细胞亚群产生的IL-17增加，血清骨桥蛋白(OPN)水平升高。我们证明了急性冠脉综合征患者血清中的OPN对CD4+CD45RA-FOXP3lo T细胞产生IL-17的直接影响，这种作用是通过重新募集OPN受体CD29和CD44介导的，依赖于STAT3和核激素受体维甲酸相关的孤儿受体-T(ROR？T)途径，而不是IL-6的产生。据我们所知，在急性冠脉综合征的疾病背景之外，这项研究首次证明了OPN通过增加CD4+CD45RA-FOXP3lo细胞产生IL-17而在炎症的积极调节中发挥关键作用。
Atherosclerosis is a progressive disease with a strong inflammatory component. Here we confirm the existence of a critical imbalance in the ratio of Th17 to Treg-cell populations in peripheral CD4+ T cells from patients with acute coronary syndrome (ACS), which favors inflammation. This was concurrent with increased IL-17 production from the CD4+CD45RA-FOXP3lo Treg-cell subset, and elevated osteopontin (OPN) levels in serum from ACS patients. We demonstrate a direct effect of OPN in serum from ACS patients on increased IL-17 production by CD4+CD45RA-FOXP3lo T cells, mediated through recruitment of the OPN receptors CD29 and CD44, and dependent on STAT3 and the nuclear hormone receptor retinoic-acid-related orphan receptor-?t (ROR?t) pathway, but not IL-6 production. To our knowledge and beyond the disease context of ACS, this study constitutes the first demonstration of a critical role for OPN in the positive regulation of inflammation through increased IL-17 production by CD4+CD45RA-FOXP3lo cells.