Li Weiwei, Jiao Wei, Li Fang, Liu Jinming, Hao Jie
Department of Clinical Laboratory, The Second Hospital of Hebei Medical University, Shijiazhuang, China.
Department of Cardiovascular, The Second Hospital of Hebei Medical University, Shijiazhuang, China.
Iran J Allergy Asthma Immunol. 2025 Jun 26;24(4):533-550.
Immune response is a significant mechanism in dilated cardiomyopathy (DCM). The interleukin-17 receptor (IL-17R) is crucial for immune response. A DCM model was created using doxorubicin, and IL-17R was knocked down. We assessed cardiac function, histopathological changes, fibrosis proteins, myocardial injury, and inflammation levels through echocardiography, pathological staining, immunofluorescence, and Western blot, respectively. The proportions of T cell subsets in mouse spleen tissue were identified through flow cytometry. Following these steps, we detached fibroblasts from the mouse heart and knocked down IL-17R. Angiotensin II was employed to induce cell fibrosis and co-cultured with T Helper 17 (TH17) cells. We measured inflammation, collagen deposits, and fibrosis protein expression using Sirius red staining, immunofluorescence, and Western blot. IL-17R exhibited significant expression in DCM mice. The systolic function of DCM mice significantly decreased. Myocardial fibrosis and collagen deposition in the left ventricle were markedly elevated. The levels of fibrosis proteins and pro-inflammatory factors were notably enhanced (p < 0.01). The proportion of effector CD4+ T and TH17 cells in spleen tissue noticeably increased, while the Treg cell proportion notably decreased. These indicators were significantly reversed after IL-17R knockdown. In the co-culture system, pro-inflammatory cytokines, collagen formation, and fibrosis-related protein levels increased significantly after fibrosis induction. However, the level of fibrosis and TH17/Treg cell imbalance decreased significantly after IL-17R knockdown. The knockdown of IL-17R can reduce immune reaction, which in turn improves myocardial fibrosis and alleviates DCM cardiac function.
免疫反应是扩张型心肌病（DCM）的一个重要机制。白细胞介素-17受体（IL-17R）对免疫反应至关重要。使用阿霉素建立了DCM模型，并敲低了IL-17R。我们分别通过超声心动图、病理染色、免疫荧光和蛋白质印迹评估心脏功能、组织病理学变化、纤维化蛋白、心肌损伤和炎症水平。通过流式细胞术鉴定小鼠脾脏组织中T细胞亚群的比例。经过这些步骤后，我们从小鼠心脏分离出成纤维细胞并敲低IL-17R。使用血管紧张素II诱导细胞纤维化，并与辅助性T细胞17（TH17）共培养。我们使用天狼星红染色、免疫荧光和蛋白质印迹测量炎症、胶原沉积和纤维化蛋白表达。IL-17R在DCM小鼠中表现出显著表达。DCM小鼠的收缩功能显著下降。左心室的心肌纤维化和胶原沉积明显升高。纤维化蛋白和促炎因子的水平显著增强（p<0.01）。脾脏组织中效应性CD4+T细胞和TH17细胞的比例明显增加，而调节性T细胞比例明显下降。IL-17R敲低后这些指标显著逆转。在共培养系统中，纤维化诱导后促炎细胞因子、胶原形成和纤维化相关蛋白水平显著增加。然而，IL-17R敲低后纤维化水平和TH17/Treg细胞失衡显著降低。敲低IL-17R可减少免疫反应，进而改善心肌纤维化并减轻DCM心脏功能。
