Yu Miao, Hu Jun, Zhu Ming-Xin, Zhao Tong, Liang Wei, Wen Shuang, Li Huan-Huan, Long Qi, Wang Min, Guo He-Ping, Cheng Xiang, Liao Yu-Hua, Yuan Jing
Cell Physiol Biochem. 2013;32(5):1437-50. doi: 10.1159/000356581.
Th17 cells contributed to myocardial inflammatory injury in acute viral myocarditis (AVMC), and the migration of these cells were mainly mediated by CCL20-secreting inflammatory cells. However, whether and how the resident cells such as cardiomyocytes and cardiac fibroblasts could mediate Th17 cell migration into the heart remains unclear in AVMC.
The effect of CCL20 on the dynamic alterations of intracardiac Th17 cells and disease severity were investigated through the neutralization of CCL20 in AVMC mice. The key cells releasing CCL20 in the heart and the effects of CCL20-secreting cells on Th17 cell arrest, migration and differentiation were detected in vitro.
Neutralization of CCL20 efficiently repressed the myocardial inflammation along with the reduction of Th17 cell infiltrations in the course of AVMC. In vitro, after stimulations of TNF-α, IL-1β and IL-17, cardiac fibroblasts rather than cardiomyocytes could be dominantly induced for CCL20 production. CCL20-secreting cardiac fibroblasts boosted Th17 cell arrest on endothelium, and induce Th17 cell migration. However, CCL20 produced by cardiac fibroblasts had no effect on Th17 cell differentiation and IL-17 production.
It firstly suggested that cardiac fibroblasts could recruit Th17 cells infiltration into myocardium by secreting CCL20 in AVMC.
Th17细胞在急性病毒性心肌炎（AVMC）中促成心肌炎性损伤，这些细胞的迁移主要由分泌CCL20的炎性细胞介导。然而，在AVMC中，诸如心肌细胞和心脏成纤维细胞等驻留细胞是否以及如何介导Th17细胞迁移至心脏仍不清楚。
通过在AVMC小鼠中中和CCL20，研究CCL20对心内Th17细胞动态变化及疾病严重程度的影响。在体外检测心脏中释放CCL20的关键细胞以及分泌CCL20的细胞对Th17细胞停滞、迁移和分化的影响。
在AVMC病程中，中和CCL20可有效抑制心肌炎症，同时减少Th17细胞浸润。在体外，经TNF-α、IL-1β和IL-17刺激后，心脏成纤维细胞而非心肌细胞可被显著诱导产生CCL20。分泌CCL20的心脏成纤维细胞促进Th17细胞在内皮上的停滞，并诱导Th17细胞迁移。然而，心脏成纤维细胞产生的CCL20对Th17细胞分化和IL-17产生没有影响。
首次表明在AVMC中，心脏成纤维细胞可通过分泌CCL20募集Th17细胞浸润至心肌。
