Increased expressions of IL-22 and Th22 cells in the coxsackievirus B3-Induced mice acute viral myocarditis.
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.
Department of Cardiology, First Affiliated Hospital of Guangxi Medical University, Guangxi Cardiovascular Institute, Nanning, 530021, China.
Qing
Q
Kong
Weifeng
W
Wu
Fan
F
Yang
Yanli
Y
Liu
Yimin
Y
Xue
Mengsha
M
Gao
Wenyin
W
Lai
Xiaofen
X
Pan
Yuluan
Y
Yan
Yu
Y
Pang
Yuanhua
Y
Deng
D000818:Animals; D003384:Coxsackievirus Infections / Q000276:immunology / Q000473:pathology*; D004195:Disease Models, Animal; D029822:Enterovirus B, Human / Q000276:immunology* / Q000502:physiology; D015870:Gene Expression; D007378:Interleukins / Q000378:metabolism*; D016131:Lymphocyte Subsets / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009205:Myocarditis / Q000276:immunology / Q000473:pathology*; D018123:Receptors, Interleukin / Q000096:biosynthesis; D000097043:Interleukin-22
D007378:Interleukins; D018123:Receptors, Interleukin; D000097043:Interleukin-22; C415369:interleukin-22 receptor