Tsukuba Primate Research Center, National Institutes of Biomedical Innovation, Health and Nutrition, Tsukuba 305-0843, Japan.
Department of Cardiology, Faculty of Medicine, University of Tsukuba, Tsukuba 305-8575, Japan.
Int J Mol Sci. 2021 Jan 14;22(2):794. doi: 10.3390/ijms22020794.
Dilated cardiomyopathy (DCM) is a potentially lethal disorder characterized by progressive impairment of cardiac function. Chronic myocarditis has long been hypothesized to be one of the causes of DCM. However, owing to the lack of suitable animal models of chronic myocarditis, its pathophysiology remains unclear. Here, we report a novel mouse model of chronic myocarditis induced by recombinant bacille Calmette-Guérin (rBCG) expressing a CD4 T-cell epitope of cardiac myosin heavy chain-α (rBCG-MyHCα). Mice immunized with rBCG-MyHCα developed chronic myocarditis, and echocardiography revealed dilation and impaired contraction of ventricles, similar to those observed in human DCM. In the heart, CD62LCD4 T cells were increased and produced significant amounts of IFN-γ and IL-17 in response to cardiac myosin. Adoptive transfer of CD62LCD4 T cells induced myocarditis in the recipient mice, which indicated that CD62LCD4 T cells were the effector cells in this model. rBCG-MyHCα-infected dendritic cells produced proinflammatory cytokines and induced MyHCα-specific T-cell proliferation and Th1 and Th17 polarization. This novel chronic myocarditis mouse model may allow the identification of the central pathophysiological and immunological processes involved in the progression to DCM.
扩张型心肌病（DCM）是一种潜在致命的疾病，其特征是心脏功能进行性受损。慢性心肌炎长期以来一直被认为是 DCM 的原因之一。然而，由于缺乏慢性心肌炎的合适动物模型，其病理生理学仍不清楚。在这里，我们报告了一种由表达心肌肌球蛋白重链-α（rBCG-MyHCα）CD4 T 细胞表位的重组卡介苗（rBCG）诱导的慢性心肌炎的新型小鼠模型。用 rBCG-MyHCα 免疫的小鼠发生慢性心肌炎，超声心动图显示心室扩张和收缩功能受损，类似于人类 DCM 中观察到的情况。在心脏中，CD62LCD4 T 细胞增加，并对心肌肌球蛋白产生大量 IFN-γ 和 IL-17。CD62LCD4 T 细胞的过继转移可在受体小鼠中诱导心肌炎，表明 CD62LCD4 T 细胞是该模型中的效应细胞。rBCG-MyHCα 感染的树突状细胞产生促炎细胞因子，并诱导 MyHCα 特异性 T 细胞增殖和 Th1 和 Th17 极化。这种新型慢性心肌炎小鼠模型可能有助于确定进展为 DCM 的中心病理生理和免疫学过程。
