Email updates

Keep up to date with the latest news and content from Virology Journal and BioMed Central.

Open Access Highly Accessed Research

Increased Expressions of IL-22 and Th22 cells in the coxsackievirus B3-Induced mice acute viral myocarditis

Qing Kong, Weifeng Wu*, Fan Yang, Yanli Liu, Yimin Xue, Mengsha Gao, Wenyin Lai, Xiaofen Pan, Yuluan Yan, Yu Pang and Yuanhua Deng

Author affiliations

Department of Cardiology, First Affiliated Hospital of Guangxi Medical University, Guangxi Cardiovascular Institute, Nanning, 530021, China

For all author emails, please log on.

Citation and License

Virology Journal 2012, 9:232  doi:10.1186/1743-422X-9-232

Published: 11 October 2012

Abstract

Background

Recently, a new subset of T helper (Th) cell that predominantly secret cytokine interleukin-22 (IL-22) is identified, termed Th22 cells. The Th22 subset has been demonstrated to be involved in immunity and tissue inflammation. However, the existence of Th22 cells and role of IL-22 in acute viral myocarditis (AVMC) remain unknown.

Methods

BALB/c mice were intraperitoneally (i.p) infected with CVB3 for establishing AVMC models. Control mice were treated with phosphate-buffered saline (PBS) i.p. On day 14 post injection, frequencies of splenic Th22 cells were determined, productions of IL-22 and expressions of IL-22R (IL-22 receptor) were measured. To further investigate the effects of IL-22, AVMC mice treated with Anti-IL-22 neutralizing antibody were explored. The severity of AVMC were monitored; the frequencies of Th22 cells, the expressions of IL-22 and IL-22R were investigated; in addition to IFN-γ, inflammatory cytokines IL-17, TNF-α, IL-6 as well as IL-1β, were evaluated. Cardiac viral replication were detected.

Results

Compared with control group, significant elevations of circulating Th22 cells and IL-22, cardiac protein and mRNA of IL-22, and IL-22R1 were demonstrated in AVMC group. Treatment of AVMC mice with Anti-IL-22 Ab exacerbated the severity of viral myocarditis, verified by lower survival rate, higher HW/BW ratios and cardiac pathological scores. Anti-IL-22 Ab decreased the frequencies of Th22 cells and the levels of IL-22, and increased the expressions of cardiac IL-22R1. Up-regulations of IL-17, IL-6 and TNF-α, down-regulations of IFN-γ proteins and gene expressions in the plasma and myocardium, were observed in Anti-IL-22 Ab group. Furthermore, neutralization of IL-22 significantly promoted cardiac viral replication.

Conclusions

Our data indicate that the increased frequencies of IL-22-producing Th22 cells may play an important role in the pathogenesis of CVB3-induced mice AVMC, IL-22 may act as an myocardium-protective cytokine via the IL-22–IL-22R pathway, and suggest that targeting the Th22 cell and IL-22–IL-22R pathway could provide new therapeutic modalities for the treatment of CVB3-induced AVMC.

Keywords:
Th22 cells; IL-22–IL-22R pathway; Acute viral myocarditis