| Autor: |
Li Huang, Xuedi Zhang, Junyu Fan, Xiaolei Liu, Shuhua Luo, Dianqing Cao, Youtan Liu, Zhengyuan Xia, Hanhui Zhong, Cuiping Chen, Liangqing Zhang, Zhifeng Liu, Jing Tang |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
|
| Zdroj: |
Journal of Advanced Research, Vol 44, Iss , Pp 39-51 (2023) |
| Druh dokumentu: |
article |
| ISSN: |
2090-1232 |
| DOI: |
10.1016/j.jare.2022.04.010 |
| Popis: |
Introduction: Sepsis-induced apoptosis leads to lymphopenia including the decrease of CD4+ T cells thus favoring immunosuppression. Objectives: Although epidermal growth factor receptor (EGFR) inhibitors significantly improve the survival rate of septic mice, the effect of EGFR on the function and metabolism of CD4+ T cells in sepsis remained unknown. Methods: CD4+ T cells from septic mice and patients were assessed for apoptosis, activation, Warburg metabolism and glucose transporter 1 (Glut1) expression with or without the interference of EGFR activation. Results: EGFR facilitates CD4+ T cell activation and apoptosis through Glut1, which is a key enzyme that controls glycolysis in T cells. EGFR, TANK binding kinase 1 (TBK1) and Glut1 form a complex to facilitate Glut1 transportation from cytoplasm to cell surface. Both the levels of membrane expression of EGFR and Glut1 and the activation levels of CD4+ T cells were significantly higher in patients with sepsis as compared with healthy subjects. Conclusion: Our data demonstrated that through its downstream TBK1/Exo84/RalA protein system, EGFR regulates Glut1 transporting to the cell surface, which is a key step for inducing the Warburg effect and the subsequent cellular activation and apoptosis of CD4+ T lymphocytes and may eventually affect the immune functional status, causing immune cell exhaustion in sepsis. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
|
