Effect and mechanism of T lymphocytes on human induced pluripotent stem cell-derived cardiomyocytes via Proteomics

• Published in: Stem cell research & therapy 2024-07, Vol.15 (1), p.236-14, Article 236
• Main Authors: Ye, Jin, Xu, Sichi, Liu, Xiaoqing, Zhang, Qiyu, Li, Xiao, Zhang, Hui, Ma, Jie, Leng, Ling, Zhang, Shuyang
• Format: Article
• Language: English
• Subjects: Analysis; Autoimmunity; CD4-Positive T-Lymphocytes - metabolism; Coculture Techniques; Creatine; Creatine kinase; Enzymes; Ethylenediaminetetraacetic acid; Heart cells; hiPSC-derived cardiomyocytes; Humans; Induced Pluripotent Stem Cells - cytology; Induced Pluripotent Stem Cells - metabolism; Inflammation; Medical equipment and supplies industry; Medical test kit industry; Myocarditis; Myocarditis - metabolism; Myocytes, Cardiac - cytology; Myocytes, Cardiac - metabolism; Proteome - metabolism; Proteomics; Proteomics - methods; Stem cells; T cells; T lymphocytes; T-Lymphocytes - cytology; T-Lymphocytes - metabolism
• ISSN: 1757-6512; 1757-6512
• DOI: 10.1186/s13287-024-03791-4

Abnormalities in T cell activation play an important role in the pathogenesis of myocarditis, and persistent T cell responses can lead to autoimmunity and chronic cardiac inflammation, as well as even dilated cardiomyopathy. Although previous work has examined the role of T cells in myocarditis in animal models, the specific mechanism for human cardiomyocytes has not been investigated. In this study, we constructed the human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and established the T cell-mediated cardiac injury model by co-culturing with activated CD4 + T or CD8 + T cells that were isolated from peripheral mononuclear blood to elucidate the pathogenesis of myocardial cell injury caused by inflammation. By combination of quantitative proteomics with tissue and cell immunofluorescence examination, we established a proteome profile of inflammatory myocardia from hiPSC-CMs with obvious cardiomyocyte injury and increased levels of lactate dehydrogenase content, creatine kinase isoenzyme MB and cardiac troponin. A series of molecular dysfunctions of hiPSC-CMs was observed and indicated that CD4 + cells could produce direct cardiomyocyte injury by activating the NOD-like receptor signals pathway. The data presented in our study established a proteome map of inflammatory myocardial based on hiPSC-CMs injury model. These results can provide guidance in the discovery of improved clinical treatments for myocarditis.