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ABSTRACT: 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.
SUBMITTER: Huang L
PROVIDER: S-EPMC9936423 | biostudies-literature | 2023 Feb
REPOSITORIES: biostudies-literature
Huang Li L Zhang Xuedi X Fan Junyu J Liu Xiaolei X Luo Shuhua S Cao Dianqing D Liu Youtan Y Xia Zhengyuan Z Zhong Hanhui H Chen Cuiping C Zhang Liangqing L Liu Zhifeng Z Tang Jing J
Journal of advanced research 20220501
<h4>Introduction</h4>Sepsis-induced apoptosis leads to lymphopenia including the decrease of CD4<sup>+</sup> T cells thus favoring immunosuppression.<h4>Objectives</h4>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<sup>+</sup> T cells in sepsis remained unknown.<h4>Methods</h4>CD4<sup>+</sup> T cells from septic mice and patients were assessed for apoptosis, activation, W ...[more]