Polymorphonuclear myeloid-derived suppressor cells link inflammation and damage response after trauma. Issue 6 (12th October 2021)

• Record Type: Journal Article
• Authors: Li, Xinyao; Liu, Jingping; Xing, Zhe; Tang, Jian; Sun, Hengbiao; Zhang, Xiaogang; Lv, Shuaijun; Chen, Ziyang; Shi, Mengyu; Chen, Meiqi; Zuo, Shaowen; Lyu, Xiaoming; He, Yumei
• Is Part Of: Journal of leukocyte biology. Volume 110:Issue 6(2021)
• Page Start: 1143
• Page End: 1161
• Publication Date: 2021-10-12
• Subjects: inflammation -- lectin-type oxidized LDL receptor 1 -- polymorphonuclear myeloid-derived suppressor cells -- regulation -- trauma; Leucocytes -- Periodicals; Reticulo-endothelial system -- Periodicals; 571.96
• DOI: 10.1002/JLB.3MA0821-029R
• Languages: English
• ISSNs: 0741-5400

Abstract

Abstract: Elimination of the posttraumatic inflammatory response and recovery of homeostasis are crucial for the positive prognosis of trauma patients. Myeloid-derived suppressor cells (MDSCs) are known to play a regulatory role in the posttraumatic immune response in mice, but their induction source and involved potential mechanism are poorly understood. Here, we report that polymorphonuclear MDSCs (PMN-MDSCs) are activated after trauma and are closely associated with the progression of the posttraumatic inflammatory response. In humans, lectin-type oxidized LDL receptor 1 (LOX1) was used to specifically characterize LOX1 + PMN-MDSCs. Trauma patients showed high intracellular reactive oxygen species (ROS) production, as well as activation of LOX1 + PMN-MDSCs. These MDSCs contribute to the anti-inflammatory immune response by regulating the Treg/Th17 and Th2/Th1 balances after trauma, increasing the levels of anti-inflammatory factors, and decreasing the levels of proinflammatory factors. The number of LOX1 + PMN-MDSCs was positively correlated with the positive clinical prognosis of trauma patients with infection. Activation of LOX1 + PMN-MDSCs is mediated by NF-κB signal, and TGF-β1 may be as an important inducer for LOX1 + PMN-MDSCs in the posttraumatic cytokine environment. In a pseudofracture trauma mouse model, we also observed the activation of PMN-MDSCs, accompanying high levels of intracellular ROS production, NF-κB phosphorylation, and changes in the inflammatory environment, in particularly by regulating the Treg/Th17 and Th2/Th1 balance. And more significantly, posttraumatic inflammation was alleviated in mice after transferring trauma-derived PMN-MDSCs, but aggravated after injecting with Gr1 agonistic antibody. These findings provide evidence for the specific role of PMN-MDSCs in the regulation of posttraumatic inflammation. Graphical Abstract: Role of PMN-MDSCs in the anti-inflammatory immune response by regulation of the Treg/Th17 and Th2/Th1 balances after trauma.