Original Article
 

Interleukin-17 Receptor Signaling Regulates Immune Response and Slows Down Myocardial Fibrosis in Mice with Dilated Cardiomyopathy

Abstract

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.

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Keywords
Cardiomyopathy Fibrosis Immunity Interleukin-17 T helper 17 cells

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1.
Li W, Jiao W, Li F, Liu J, Hao J. Interleukin-17 Receptor Signaling Regulates Immune Response and Slows Down Myocardial Fibrosis in Mice with Dilated Cardiomyopathy. Iran J Allergy Asthma Immunol. 2025;:1-19.