IL-22-producing Th22 cells play a protective role in CVB3-induced chronic myocarditis and dilated cardiomyopathy by inhibiting myocardial fibrosis.
IL-22-producing Th22 cells play a protective role in CVB3-induced chronic myocarditis and dilated cardiomyopathy by inhibiting myocardial fibrosis.
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产生IL-22的Th22细胞通过抑制心肌纤维化在CVB3诱导的慢性心肌炎和扩张型心肌病中发挥保护作用
DOI：
10.1186/s12985-014-0230-z
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发表时间：
2014-12-30
期刊：
影响因子：
4.8
通讯作者：
Zhou Q
中科院分区：
文献类型：
--
作者：
Guo Y;Wu W;Cen Z;Li X;Kong Q;Zhou Q
背景最近发现了一种新的辅助性T细胞亚群，称为产生IL-22的Th22细胞。Th22细胞与免疫和炎症有关。然而，这些细胞在从急性病毒性心肌炎(AVMC)到扩张型心肌病(DCM)和心肌纤维化进展中的作用尚不清楚。感染柯萨奇B3病毒(CVB3)，建立AVMC、慢性心肌炎和扩张型心肌炎模型。分别于注射后2、12、24周检测脾Th22细胞百分率、血浆IL-22水平、心脏IL-22受体(IL-22R)表达及心肌纤维化指标。此外，用抗IL-22中和抗体(Ab)治疗患有AVMC和慢性心肌炎的小鼠。结果与相同时间点的对照组比较，AVMC、慢性心肌炎和DCM组小鼠脾Th22细胞百分率、血浆IL-22水平、心肌IL-22R表达和心肌纤维化指标均显著升高，血浆IL-22水平升高，心脏IL-22R升高，I型胶原(COL1-A1)、III型胶原(COL3-A1)和基质金属蛋白酶-9(MMP9)表达增加。而基质金属蛋白酶组织抑制因子-1(TIMP-1)表达下降。用抗IL-22单抗治疗AVMC和慢性心肌炎小鼠可降低存活率并加重心肌纤维化。抗IL-22单抗治疗组小鼠的脾Th22细胞百分率、血浆IL-22水平和心脏IL-22R表达水平也低于AVMC和慢性心肌炎小鼠的免疫球蛋白G和PBS治疗组。结论Th22细胞在CVB3诱导的小鼠慢性心肌炎和扩张性心肌炎的发病机制中起重要作用。IL-22是一种通过抑制心肌纤维化而保护心肌的细胞因子。因此，Th22细胞可作为DCM的潜在治疗靶点。
BackgroundA new subset of T helper (Th) cells, named IL-22-producing Th22 cells, was identified recently. Th22 cells have been implicated in immunity and inflammation. However, the role of these cells in the progression from acute viral myocarditis (AVMC) to dilated cardiomyopathy (DCM) and myocardial fibrosis remains unknown.MethodsBALB/c mice were repeatedly i.p. infected with Coxsackie virus B3 (CVB3) to establish models of AVMC, chronic myocarditis and DCM. On week 2, 12 and 24 post initial injection, the percentage of splenic Th22 cells, the levels of plasma IL-22, cardiac IL-22 receptor (IL-22R) expression, and indicators of myocardial fibrosis were measured. Further, mice with AVMC and chronic myocarditis were treated with an anti-IL-22 neutralizing antibody (Ab). The collagen volume fraction (CVF), the percentage of splenic Th22 cells, plasma IL-22 levels, cardiac IL-22R expression and indicators of myocardial fibrosis were then monitored.ResultsCompared to control mice at the same time points, AVMC, chronic myocarditis and DCM mice have higher percentage of splenic Th22 cells, higher plasma IL-22 levels, increased cardiac IL-22R, as well as increased collagen typeI-A1 (COL1-A1), collagen type III-A1 (COL3-A1) and matrix metalloproteinase-9 (MMP9) expression. However, the expression of tissue inhibitor of metalloproteinase-1(TIMP-1) was decreased. Treatment of AVMC and chronic myocarditis mice with an anti-IL-22 Ab decreased the survival rate and exacerbated myocardial fibrosis. The percentage of splenic Th22 cells, plasma IL-22 levels and cardiac IL-22R expression also decreased in anti-IL-22 Ab treatment group as compared to IgG and PBS treated groups of AVMC and chronic myocarditis mice. Moreover, increased expression of COL1-A1, COL3-A1, MMP9 but decreased expression of TIMP-1 were observed in anti-IL-22 Ab mouse group.ConclusionsTh22 cells play an important role in the pathogenesis of CVB3-induced mouse chronic myocarditis and DCM. IL-22 is a myocardium-protective cytokine by inhibiting myocardial fibrosis. Therefore, Th 22 cells may be considered as potential therapeutic targets for DCM.
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