Cui Dawei, Zhong Fengyun, Lin Jie, Wu Yidong, Long Quan, Yang Xianzhi, Zhu Qiaoyun, Huang Li, Mao Qifen, Huo Zhaoxia, Zhou Zhe, Xie Guoliang, Zheng Shufa, Yu Fei, Chen Yu
Department of Laboratory Medicine, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
Key Laboratory of Clinical In Vitro Diagnostic Techniques of Zhejiang Province, Hangzhou, China.
Oncotarget. 2017 Apr 25;8(17):29370-29382. doi: 10.18632/oncotarget.14083.
Interleukin (IL)-22+CD4+T (Th22) cells play crucial roles in the pathogenesis of autoimmune diseases and infectious diseases, although the role of Th22 cells remains largely unclear in children with hand, foot, and mouth disease (HFMD) caused by enterovirus 71 (EV71). This study aims to explore the role of circulating IL-22+IL-17A-CD4+T (cTh22) cells in children with EV71-associated HFMD. We found that during the acute stage of illness, the frequencies of cTh22 and circulating IL-22+IL-17A+CD4+T (IL-22+cTh17) cells in CD4+T cells infrom affected patients, and especially in severely affected patients, were significantly higher than in healthy controls (HC). The major source of IL-22 production was cTh22 cells, partially from cTh17 cells. Moreover, the protein and mRNA levels of IL-22, IL-17A, IL-23, IL-6, and TNF-α were significantly different among the mild patients, severe patients and HC, as well as AHR and RORγt mRNA levels. A positive correlation was found between plasma IL-22 levels and cTh22 cell frequencies, and cTh17 cell and IL-22+ cTh17 cell frequencies. Furthermore, the frequencies of cTh22 were significantly decreased in the convalescent patients. Our findings indicated that cTh22 cells could play critical roles in the pathogenesis of EV71 infection, and are potential therapeutic targets for patients with EV71-associated HFMD.
白细胞介素（IL）-22⁺CD4⁺T（Th22）细胞在自身免疫性疾病和感染性疾病的发病机制中起关键作用，尽管在由肠道病毒71型（EV71）引起的手足口病（HFMD）患儿中Th22细胞的作用仍不清楚。本研究旨在探讨循环IL-22⁺IL-17A⁻CD4⁺T（cTh22）细胞在EV71相关HFMD患儿中的作用。我们发现，在疾病急性期，受影响患者尤其是重症患者CD4⁺T细胞中cTh22细胞和循环IL-22⁺IL-17A⁺CD4⁺T（IL-22⁺cTh17）细胞的频率显著高于健康对照（HC）。IL-22产生的主要来源是cTh22细胞，部分来自cTh17细胞。此外，轻度患者、重度患者和HC之间，IL-22、IL-17A、IL-23、IL-6和TNF-α的蛋白质和mRNA水平以及AHR和RORγt mRNA水平存在显著差异。血浆IL-22水平与cTh22细胞频率、cTh17细胞和IL-22⁺cTh17细胞频率之间存在正相关。此外，恢复期患者cTh22细胞频率显著降低。我们的研究结果表明，cTh22细胞可能在EV71感染的发病机制中起关键作用，是EV71相关HFMD患者潜在的治疗靶点。
