Liu Qinxin, Wang Yuchang, Zheng Qiang, Dong Xijie, Xie Zhenxing, Panayi Adriana, Bai Xiangjun, Li Zhanfei
Department of Traumatic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Division of Plastic Surgery, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Department of Traumatic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Life Sci. 2021 Aug 1;278:119626. doi: 10.1016/j.lfs.2021.119626. Epub 2021 May 15.
Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. The majority of sepsis-related deaths occur during late sepsis, which presents as a state of immunosuppression. Myeloid-derived suppressor cells (MDSCs) have been reported to promote immunosuppression during sepsis. Here we aim to understand the role of microRNAs in regulating MDSCs proliferation and immunosuppression function during sepsis.
Murine sepsis model was established using cecal ligation and puncture (CLP). A microarray was used to identify microRNAs with differential expression in murine sepsis. The effect of microRNA-150 on MDSCs proliferation and function was then evaluated. 140 multiple trauma patients from Tongji Hospital and 10 healthy controls were recruited. Peripheral blood samples were taken and the serum level of miR-150 was measured.
In the murine model of sepsis, MDSCs expansion was noted in the spleen and bone marrow, while expression of miR-150 in MDSCs decreased. Replenishing miR-150 inhibited the expansion of MDSCs in both monocytic and polymorphonuclear subpopulations, as well as decreasing the immunosuppressive function of MDSCs, through down-regulation of ARG1. Both pro-inflammatory cytokine IL-6 and anti-inflammatory cytokines TGF-β and IL-10 were reduced by miR-150. In human, the serum level of miR-150 was down-regulated in septic patients and elevated in non-septic trauma patients compared to healthy controls.
Our study showed that MiR-150 is down-regulated during sepsis. Replenishing miR-150 reduces the immunosuppression function of MDSCs by down-regulating ARG1 in late sepsis. MiR-150 might serve as a potential therapeutic option for sepsis.
脓毒症被定义为由宿主对感染的失调反应引起的危及生命的器官功能障碍。大多数与脓毒症相关的死亡发生在晚期脓毒症期间，其表现为免疫抑制状态。据报道，髓源性抑制细胞（MDSCs）在脓毒症期间促进免疫抑制。在此，我们旨在了解微小RNA在脓毒症期间调节MDSCs增殖和免疫抑制功能中的作用。
采用盲肠结扎和穿刺（CLP）建立小鼠脓毒症模型。使用微阵列鉴定小鼠脓毒症中差异表达的微小RNA。然后评估微小RNA-150对MDSCs增殖和功能的影响。招募了140名来自同济医院的多发伤患者和10名健康对照。采集外周血样本并测量血清miR-150水平。
在小鼠脓毒症模型中，脾脏和骨髓中出现MDSCs扩增，而MDSCs中miR-150的表达降低。补充miR-150可抑制单核细胞和多形核亚群中MDSCs的扩增，并通过下调ARG1降低MDSCs的免疫抑制功能。促炎细胞因子IL-6以及抗炎细胞因子TGF-β和IL-10均被miR-150降低。在人类中，与健康对照相比，脓毒症患者血清miR-150水平下调，非脓毒症创伤患者血清miR-150水平升高。
我们的研究表明，脓毒症期间MiR-150下调。在晚期脓毒症中，补充miR-150通过下调ARG1降低MDSCs的免疫抑制功能。MiR-150可能是脓毒症的一种潜在治疗选择。
