Department of Clinical Laboratory, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Eur J Immunol. 2012 Oct;42(10):2803-14. doi: 10.1002/eji.201242475. Epub 2012 Aug 28.
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(-) FOXP3(lo) 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(-) FOXP3(lo) 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-γt (RORγt) 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(-) FOXP3(lo) cells.
动脉粥样硬化是一种具有强烈炎症成分的进行性疾病。在这里，我们证实了急性冠脉综合征（ACS）患者外周血 CD4(+)T 细胞中 Th17 与 Treg 细胞比例失衡，这有利于炎症的发生。这与 CD4(+)CD45RA(-)FOXP3(lo)Treg 细胞亚群中 IL-17 的产生增加以及 ACS 患者血清中骨桥蛋白（OPN）水平升高同时发生。我们证明了 ACS 患者血清中的 OPN 可直接作用于 CD4(+)CD45RA(-)FOXP3(lo)T 细胞，增加 IL-17 的产生，这是通过募集 OPN 受体 CD29 和 CD44 介导的，依赖于 STAT3 和核激素受体维甲酸相关孤儿受体-γt（RORγt）途径，但不依赖于 IL-6 的产生。就我们所知，在 ACS 的疾病背景之外，本研究首次证明了 OPN 在通过 CD4(+)CD45RA(-)FOXP3(lo)细胞增加 IL-17 的产生来正向调节炎症中具有关键作用。
