Ochoa-Espinosa Amanda, Genty Lucile, Xu Lifen, Akin Asli, Glatz Katharina, Decembrini Sarah, Mueller Christian, Neutzner Albert, Jayachandran Rajesh, Mahfoud Felix, Pieters Jean, Kaufmann Beat A
Department of Biomedicine, University of Basel, Basel, Switzerland.
Department of Pathology, University Hospital and University of Basel, Basel, Switzerland.
ESC Heart Fail. 2025 Jul 22. doi: 10.1002/ehf2.15384.
Dilated cardiomyopathy (DCM) caused by viral myocarditis and autoimmune processes is a frequent cause for heart failure. CD4+ T cells are indispensable for autoimmune myocarditis. Coronin 1 is required for peripheral T cell survival. We therefore hypothesized that deficiency in coronin 1 protects mice from experimental autoimmune myocarditis (EAM).
EAM was induced in coronin 1-deficient and wild-type (WT) mice. WT CD4+ T cells isolated from spleens were transferred to coronin 1-deficient mice in a subset of animals; IL-10 was blocked in another subset before EAM induction. On day 21 mice underwent echocardiography and were sacrificed. Myocarditis severity was scored (Grades 0-4) on histology. Leukocyte fractions in blood and heart tissue were characterized. Plasma cytokines including interleukin (IL)-10 were measured and RNA sequencing of myocardial tissue was performed.
The severity of myocarditis was lower in coronin 1-deficient versus WT mice [median 0 (25th-75th percentile 0-2) vs. 4 (3-4), P < 0.0001]. Coronin 1-deficient animals showed significant reductions of inflammatory cells in the myocardium [median 2.5% (25th-75th percentile 1.5%-7.0%) vs. 28.3% (14.5%-54.8%), P < 0.0001]. IL-10 was selectively increased in the plasma of coronin 1-deficient mice [median 3.0 pg/mL (25th-75th percentile 1.3-5.2 pg/mL) vs. 0.4 pg/mL (0-2.0 pg/mL), P < 0.05]. Transfer of WT CD4+ T cells but not blocking of IL-10 restored EAM. Left ventricular mass was increased, but effects of myocarditis on left ventricular function were evident only on the RNA level.
Deficiency in coronin 1 protects from the development of EAM by reducing CD4+ T cells. This protection resulted in less structural alterations of the left ventricular myocardium. IL-10 was selectively increased in the plasma of coronin 1-deficient mice, but blocking of IL-10 was not sufficient to restore EAM.
由病毒性心肌炎和自身免疫过程引起的扩张型心肌病（DCM）是心力衰竭的常见原因。CD4 + T细胞对于自身免疫性心肌炎不可或缺。冠蛋白1是外周T细胞存活所必需的。因此，我们假设冠蛋白1缺乏可保护小鼠免受实验性自身免疫性心肌炎（EAM）的侵害。
在冠蛋白1缺陷型和野生型（WT）小鼠中诱导EAM。从脾脏分离的WT CD4 + T细胞被转移到一部分动物的冠蛋白1缺陷型小鼠中；在另一部分动物中，在诱导EAM之前阻断IL-10。在第21天，对小鼠进行超声心动图检查并处死。通过组织学对心肌炎严重程度进行评分（0-4级）。对血液和心脏组织中的白细胞组分进行表征。测量包括白细胞介素（IL）-10在内的血浆细胞因子，并对心肌组织进行RNA测序。
与WT小鼠相比，冠蛋白1缺陷型小鼠的心肌炎严重程度较低[中位数0（第25-75百分位数0-2）对4（3-4），P <0.0001]。冠蛋白1缺陷型动物的心肌中炎症细胞显著减少[中位数2.5%（第25-75百分位数1.5%-7.0%）对28.3%（14.5%-54.8%），P <0.0001]。冠蛋白1缺陷型小鼠血浆中的IL-10选择性增加[中位数3.0 pg/mL（第25-75百分位数1.3-5.2 pg/mL）对0.4 pg/mL（0-2.0 pg/mL），P <0.05]。WT CD4 + T细胞的转移而非IL-10的阻断恢复了EAM。左心室质量增加，但心肌炎对左心室功能的影响仅在RNA水平上明显。
冠蛋白1缺乏通过减少CD4 + T细胞来保护免受EAM的发展。这种保护导致左心室心肌的结构改变较少。冠蛋白1缺陷型小鼠血浆中的IL-10选择性增加，但阻断IL-10不足以恢复EAM。
