Bcl2-Like Protein 12 Is Required for the Aberrant T Helper-2 Polarization in the Heart by Enhancing Interleukin-4 Expression and Compromising Apoptotic Machinery in CD4+ T Cells
| Autor: | Ping-Chang Yang, Xiao Chen, Man Rao, Xian-Hai Zeng, Liang Chen, Ningning Zhang, Mangyuan Wang, Jiangping Song |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Adult CD4-Positive T-Lymphocytes Cardiomyopathy Dilated Male Myocarditis Inflammation Apoptosis GATA3 Transcription Factor 03 medical and health sciences Mice 0302 clinical medicine Th2 Cells Physiology (medical) medicine Animals Humans Promoter Regions Genetic Interleukin 4 Mice Inbred BALB C business.industry Myocardium T lymphocyte Middle Aged medicine.disease Cell biology 030104 developmental biology T helper 2 Proto-Oncogene Proteins c-bcl-2 030220 oncology & carcinogenesis Cytokines Female Interleukin-4 medicine.symptom Tumor Suppressor Protein p53 Cardiology and Cardiovascular Medicine business |
| Zdroj: | Circulation. 138(22) |
| ISSN: | 1524-4539 |
| Popis: | Background: The biased T helper-2 (Th2) response plays a critical role in myocarditis. Bcl2-like protein 12 (Bcl2L12) is associated with the Th2 pattern of inflammation. This study aims to elucidate the role of Bcl2L12 in the pathogenesis of Th2-biased inflammation in the heart. Methods: Mice were treated with the myosin heavy-chain-α peptides to induce inflammation in the heart. Human hearts were collected from the surgically removed hearts of patients who had undergone heart transplantation. Results: The expression of Bcl2L12 was detected in CD4 + T cells of the hearts, which was markedly higher in the hearts with myocarditis at the advanced stage of heart failure compared with the control (dilated cardiomyopathy) hearts without myocarditis. Mice with Bcl2L12-deficient CD4 + T cells failed to induce the Th2-biased inflammation in the heart. CD4 + T cells with a higher expression of Bcl2L12 were prone to differentiate into Th2 cells. Bcl2L12 formed a complex with GATA3 in CD4 + T cells to enhance the binding between GATA3 and the Il4 promoter, which promoted the Il4 gene transcription. Bcl2L12 compromised the apoptotic machinery by inhibiting the expression of p53 in CD4 + T cells to reduce the activation-induced CD4 + T cell death. Conclusions: CD4 + T cells isolated from hearts with myocarditis at the end stage of heart failure express high levels of Bcl2L12, and the latter is required for the development of aberrant Th2 polarization in the heart. The Bcl2L12 may be a novel target in the treatment of myocarditis as well as other Th2-biased inflammation. |
| Databáze: | OpenAIRE |
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