Increased expressions of IL-22 and Th22 cells in the coxsackievirus B3-Induced mice acute viral myocarditis.
Increased expressions of IL-22 and Th22 cells in the coxsackievirus B3-Induced mice acute viral myocarditis.
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柯萨奇病毒B3诱导的小鼠急性病毒性心肌炎中IL-22和Th22细胞表达增加
DOI：
10.1186/1743-422x-9-232
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发表时间：
2012-10-11
期刊：
影响因子：
4.8
通讯作者：
Deng Y
中科院分区：
文献类型：
--
作者：
Kong Q;Wu W;Yang F;Liu Y;Xue Y;Gao M;Lai W;Pan X;Yan Y;Pang Y;Deng Y
背景最近，一个新的辅助性T细胞(Th)亚群被发现，它主要是分泌细胞因子IL-22，称为Th22细胞。Th22亚群已被证明与免疫和组织炎症有关。然而，Th22细胞的存在以及IL-22在急性病毒性心肌炎(AVMC)中的作用尚不清楚。对照组小鼠腹腔注射磷酸盐缓冲盐水(PBS)。注射后第14天，检测小鼠脾Th22细胞频率、IL-22的产生及IL-22R的表达。为了进一步研究IL-22的作用，用抗IL-22中和抗体处理AVMC小鼠。观察患者病情严重程度，检测Th2 2细胞百分率、IL-22及IL-22R的表达，并检测炎性细胞因子IL-17、肿瘤坏死因子-α、IL-6及IL-1β的表达。结果与对照组比较，AVMC组大鼠外周血中Th22细胞、IL-22、心肌组织中IL-22蛋白、IL-22mRNA及IL-22R1均显著升高。用抗IL-22单抗治疗AVMC小鼠可加重病毒性心肌炎的严重程度，表现为存活率降低、HW/BW比值升高和心脏病理评分升高。抗IL-22单抗可降低Th22细胞百分率和IL-22水平，增加心脏IL-22R1的表达。抗IL-22单抗组IL-17、IL-6和肿瘤坏死因子-α表达上调，干扰素-γ蛋白和基因表达下调。结论产生IL-22的Th22细胞频率增加可能在CVB3诱导的小鼠AVMC的发病机制中起重要作用，IL-22可能通过IL-22-IL-22R途径发挥心肌保护细胞因子的作用，提示靶向Th22细胞和IL-22-IL-22R通路可为CVB3诱导的AVMC的治疗提供新的治疗途径。
BackgroundRecently, 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.MethodsBALB/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.ResultsCompared 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.ConclusionsOur 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.