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ELF4 improves sepsis-induced myocardial injury by regulating STING signaling-mediated T cells differentiation

Year: 2025

Type: article

Abstract: Septic cardiomyopathy (SCM) is a common complication caused by sepsis. T cells differentiation is involved in SCM progression. However, the role and underlying mechanisms of T cells-mediated immunity in SCM remain unclear. This study aimed to investigate the role of STING-mediated T cells differentiation in SCM. Cecal ligation and puncture (CLP) surgery was conducted in mice to establish SCM model. The mice were injected intraperitoneally with STING agonist ADU-S100 and C-176 after modeling. Wild type (WT) mice and CD4-STING-/- mice were employed. Besides, overexpressing vectors of ELF4 (oe-ELF4), short hairpin RNA targeting ELF4 (sh-ELF4) were transfected into 293T cells. STING signaling was found to be activated in sepsis-induced myocardial immune injury in mice. The administration of ADU-S100 exacerbated myocardial injury and inflammation, while C-176 alleviated these effects. Additionally, STING activation influenced T cells differentiation, with an increase in Th1 and Th17 cells and a decrease in Treg cells. Conditional knockout of STING in CD4+ T cells reduced Th1 and Th17 populations and improved myocardial function and histology. Furthermore, ELF4 was found to inhibit STING activation, reducing T cells differentiation into pro-inflammatory subsets. Overexpression of ELF4 in CD4+ T cells ameliorated myocardial damage and improved cardiac function in CLP mice, suggesting that the ELF4-STING signaling axis plays a protective role in sepsis-induced myocardial injury by regulating T cells differentiation. 1. Activation of STING signaling pathway exacerbated sepsis-induced myocardial injury in mice. 2. STING signaling enhanced pro-inflammatory T cells differentiation and contribute to sepsis-induced myocardial damage in mice. 3. ELF4 directly interacted with STING and negatively regulated its activation. 4. Overexpression of ELF4 ameliorated myocardial injury by regulating STING mediated T cells differentiation.

Source: Cell Biology and Toxicology

DOI: 10.1007/s10565-025-10029-3

Authors: Yawen Zheng, Xiongjun Peng, Yusha Zhang, Ruilin Liu, Junke Long

Institutions: Central South University, Xiangya Hospital Central South University, Second Xiangya Hospital of Central South University

Language: English

Topic: Sepsis Diagnosis and Treatment

Subfield: Epidemiology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $4,190