Zhang Yaolu, Lian Jie, Zhu Lujia, Wei Yamei, Wang Kaikai, Lu Zhongqiu, Chen Longwang
Emergency Department, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China.
Wenzhou Key Laboratory of Emergency and Disaster Medicine, Wenzhou, 325000, China.
Inflammation. 2025 Jul 17. doi: 10.1007/s10753-025-02333-1.
MicroRNA-182 (miR-182) exhibits immunomodulatory effects in regulating inflammatory responses to bacterial infection. However, the involvement of miR-182 in regulating T-cell immune function and differentiation in sepsis remains unknown. This study investigated the role of miR-182 in regulating T cell immune function and its mechanism in sepsis-induced immunosuppression. Using the cecum ligation and puncture model to mimic experimental sepsis, we found a significant reduction in splenic lymphocyte numbers and dysregulated T cell differentiation in septic mice. miR-182 expression was elevated in septic mice. Its knockout improved T cell immune function, ameliorated organ damage and improved survival rates in septic mice. Metabolomic and proteomic profiling revealed that histidine catabolism was attenuated and histidine was increased after miR-182 knockout. L-histidine supplementation alleviated T-cell immunosuppression in vivo. In addition, elevated plasma miR-182 levels were correlated with poor clinical prognosis in sepsis patients. Our findings demonstrate that miR-182 deficiency ameliorates the immunosuppression of T cells through the modulation of histidine metabolism, offering novel insights into the molecular mechanisms underlying T-cell dysfunction in sepsis.
微小RNA-182（miR-182）在调节对细菌感染的炎症反应中表现出免疫调节作用。然而，miR-182在脓毒症中调节T细胞免疫功能和分化的作用仍不清楚。本研究探讨了miR-182在调节T细胞免疫功能中的作用及其在脓毒症诱导的免疫抑制中的机制。使用盲肠结扎和穿刺模型模拟实验性脓毒症，我们发现脓毒症小鼠的脾脏淋巴细胞数量显著减少，T细胞分化失调。脓毒症小鼠中miR-182表达升高。其敲除改善了脓毒症小鼠的T细胞免疫功能，减轻了器官损伤并提高了存活率。代谢组学和蛋白质组学分析表明，miR-182敲除后组氨酸分解代谢减弱，组氨酸增加。补充L-组氨酸可减轻体内T细胞免疫抑制。此外，脓毒症患者血浆miR-182水平升高与不良临床预后相关。我们的研究结果表明，miR-182缺乏通过调节组氨酸代谢改善T细胞免疫抑制，为脓毒症中T细胞功能障碍的分子机制提供了新的见解。
