Zheng Yawen, Peng Xiongjun, Zhang Yusha, Liu Ruilin, Long Junke
National Clinical Research Center for Geriatric Disorders, Xiangya Hospital of Central South University, Changsha City, Hunan Province, China.
Department of Social Affairs, The Second Xiangya Hospital of Central South University, Changsha City, Hunan Province, China.
Cell Biol Toxicol. 2025 May 7;41(1):82. doi: 10.1007/s10565-025-10029-3.
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.
脓毒症性心肌病（SCM）是脓毒症引起的常见并发症。T细胞分化参与SCM的进展。然而，T细胞介导的免疫在SCM中的作用及潜在机制仍不清楚。本研究旨在探讨STING介导的T细胞分化在SCM中的作用。对小鼠进行盲肠结扎和穿刺（CLP）手术以建立SCM模型。建模后，给小鼠腹腔注射STING激动剂ADU-S100和C-176。使用野生型（WT）小鼠和CD4-STING小鼠。此外，将ELF4的过表达载体（oe-ELF4）、靶向ELF4的短发夹RNA（sh-ELF4）转染到293T细胞中。研究发现，在小鼠脓毒症诱导的心肌免疫损伤中STING信号被激活。给予ADU-S100加剧了心肌损伤和炎症，而C-176减轻了这些影响。此外，STING激活影响T细胞分化，Th1和Th17细胞增加，调节性T细胞减少。CD4 T细胞中STING的条件性敲除减少了Th1和Th17细胞群，改善了心肌功能和组织学。此外，发现ELF4抑制STING激活，减少T细胞分化为促炎亚群。在CLP小鼠的CD4 T细胞中过表达ELF4可改善心肌损伤并改善心脏功能，这表明ELF4-STING信号轴通过调节T细胞分化在脓毒症诱导的心肌损伤中起保护作用。
