Changes of circulating Th22 cells in children with hand, foot, and mouth disease caused by enterovirus 71 infection.

Dawei Cui,Fengyun Zhong,Fei Yu,Li Huang,Qiaoyun Zhu,Jie Lin,Shufa Zheng,Zhe Zhou,Yidong Wu,Qifen Mao,Quan Long,Guoliang Xie,Zhaoxia Huo,Yu Chen,Xianzhi Yang

doi:10.18632/oncotarget.14083

Abstract

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.

Highlights

Hand, foot and mouth disease (HFMD) is a common infectious disease in young children, and outbreaks occur annually worldwide [1,2]
We reported that the frequencies of circulating IL-22+IL-17A-CD4+T cells, circulating IL-17A+CD4+T cells and IL-22+IL17A+CD4+T cells (IL-22+circulating Th17 cell (cTh17)) in CD4+T cells from peripheral blood mononuclear cells (PBMCs) during the acute stage of children with Enterovirus 71 (EV71)-associated HFMD were significantly increased compared to healthy controls (HC); the percentages of circulating Th22 (cTh22), IL-22+cTh17 and cTh17 cells in the mild cases of HFMD were notably decreased compared to the severe cases
Foot, and mouth disease (HFMD) is a common childhood illness caused by serotypes of the Previous studies have indicated that both cellular and humoral immune responses, such as B cells and T cells including IL-17A-producing Th cell (Th17), Th1, Th2, and CD8+T cells, EV71antibody, and associated cytokines play important roles in animal models with EV71 infection [4, 15, 16]

Summary

Introduction

Foot and mouth disease (HFMD) is a common infectious disease in young children, and outbreaks occur annually worldwide [1,2]. There are over one million HFMD cases in the world and 200 cases of mortality since 2008, and approximately 9 million cases of HFMD have been reported between 2008 and 2013 in China [35]. Enterovirus 71 (EV71) is one of the most common etiologies of HFMD, and EV71-associated HFMD has been increasingly reported in Asia-Pacific regions such as Malaysia, Japan, Singapore, China, and South Korea among young children less than five years of age since 1997 [6,7,8,9,10]. EV71 infection is a serious and growing public health issue in the world. The pathogenesis of severe HFMD caused by EV71 infection remains unknown. The disorders of cellular and humoral immune responses may play important roles in the pathogenesis of EV71-related severe diseases

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