Institute of Immunobiology, Kantonal Hospital St. Gallen, St. Gallen, Switzerland.
Eur J Immunol. 2012 Sep;42(9):2311-21. doi: 10.1002/eji.201142209. Epub 2012 Jul 13.
Myocarditis is a potentially lethal inflammatory heart disease of children and young adults that frequently leads to dilated cardiomyopathy (DCM). Since diagnostic procedures and efficient therapies are lacking, it is important to characterize the critical immune effector pathways underlying the initial cardiac inflammation and the transition from myocarditis to DCM. We describe here a T-cell receptor (TCR) transgenic mouse model with spontaneously developing autoimmune myocarditis that progresses to lethal DCM. Cardiac magnetic resonance imaging revealed early inflammation-associated changes in the ventricle wall including transient thickening of the left ventricle wall. Furthermore, we found that IFN-γ was a major effector cytokine driving the initial inflammatory process and that the cooperation of IFN-γ and IL-17A was essential for the development of the progressive disease. This novel TCR transgenic mouse model permits the identification of the central pathophysiological and immunological processes involved in the transition from autoimmune myocarditis to DCM.
心肌炎是一种潜在致命的儿童和青年人群的炎性心脏疾病，常导致扩张型心肌病（DCM）。由于缺乏诊断程序和有效的治疗方法，因此描述潜在的关键免疫效应途径对于理解初始心脏炎症和从心肌炎向 DCM 的转变非常重要。我们在此描述了一种 T 细胞受体（TCR）转基因小鼠模型，该模型具有自发性自身免疫性心肌炎，进展为致命的 DCM。心脏磁共振成像显示心室壁的早期炎症相关变化，包括左心室壁的短暂增厚。此外，我们发现 IFN-γ 是驱动初始炎症过程的主要效应细胞因子，IFN-γ 和 IL-17A 的合作对于进行性疾病的发展至关重要。这种新型 TCR 转基因小鼠模型可用于鉴定从自身免疫性心肌炎向 DCM 转变涉及的核心病理生理和免疫学过程。
