EGFR promotes the apoptosis of CD4+ T lymphocytes through TBK1/Glut1 induced Warburg effect in sepsis.

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.

• Authors: 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
• Journal: Journal of advanced research (J Adv Res) Vol. 44 Pg. 39-51 (02 2023) ISSN: 2090-1224 [Electronic] Egypt
• PMID: 35618635 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2022. Production and hosting by Elsevier B.V.

Chemical References

• ErbB Receptors
• Tbk1 protein, mouse
• Protein Serine-Threonine Kinases

Topics

• Animals
• Mice
• CD4-Positive T-Lymphocytes (metabolism)
• ErbB Receptors (metabolism, pharmacology)
• Apoptosis
• Sepsis (metabolism)
• Protein Serine-Threonine Kinases (metabolism)