From the Department of Anaesthesiology (L.D., X.Z., K.W., H.Z.), Harbin Medical University Cancer Hospital; and Department of Pain (G.W.), Research Institute of Heilongjiang Academy of Medical Sciences, Heilongjiang, China.
J Trauma Acute Care Surg. 2018 Sep;85(3):549-559. doi: 10.1097/TA.0000000000001903.
The T-helper 17 (Th17)/regulatory T (Treg) cell balance is essential for immune homeostasis. However, the effects of gastric surgery on this balance remain unclear. The aim of present study is to identify the influence of gastric surgery on Th17/Treg cell balance and the role of programmed death 1 (PD-1)/programmed cell death-ligand 1 (PD-L1) pathway in this process.
Mice were divided into control, sham, and surgery group randomly. Animals in surgery group accepted partial gastrectomy. Mice in sham group only received laparotomy without partial gastrectomy. Then, we detected the percentages of Treg and Th17 cells, the expression of fork-head/winged helix transcription factor (Foxp3) and retinoic acid-related orphan receptor γt (RORγt) in splenocytes, as well as plasma levels of transforming growth factor (TGF)-β1 and interleukin (IL)-17 on Days 1, 3, 5, 7 after surgery. We also analyzed the expression of PD-1 and PD-L1. The roles of PD-1/PD-L1 on the Th17/Treg balance were evaluated by the induction of Th17 or Treg cells in the presence or absence of PD-1 antibody and recombinant PD-L1 immunoglobulin (Ig) in vitro.
The percentage of Treg cells increased, accompanied with elevated expression of Foxp3 and TGF-β1 (p < 0.05), whereas the percentage of Th17 cells and the expression of RORγt and IL-17 decreased in mice that underwent partial gastrectomy (p < 0.05). The levels of PD-1 and PD-L1 were higher in surgery group than those in control and sham groups (p < 0.05). In vitro, the polarization of Th17 cells was enhanced, and the polarization of Treg cells was inhibited in anti-PD-1 treatment group compared with that in isotype group (p < 0.05).
Partial gastrectomy resulted in Th17/Treg imbalance, and increased the expression of PD-1 and PD-L1. blockade of PD-1/PD-L1 pathway alleviated gastric surgery-induced imbalance of Th17/Treg cells.
辅助性 T 细胞 17（Th17）/调节性 T（Treg）细胞平衡对于免疫稳态至关重要。然而，胃手术对这种平衡的影响尚不清楚。本研究旨在确定胃手术对 Th17/Treg 细胞平衡的影响以及程序性死亡 1（PD-1）/程序性死亡配体 1（PD-L1）通路在这一过程中的作用。
将小鼠随机分为对照组、假手术组和手术组。手术组接受部分胃切除术。假手术组仅接受剖腹术而不进行部分胃切除术。然后，我们检测了手术后第 1、3、5、7 天脾细胞中 Treg 和 Th17 细胞的百分比、叉头/翅膀螺旋转录因子（Foxp3）和维甲酸相关孤儿受体γt（RORγt）的表达以及转化生长因子（TGF）-β1 和白细胞介素（IL）-17 的血浆水平。我们还分析了 PD-1 和 PD-L1 的表达。通过在存在或不存在 PD-1 抗体和重组 PD-L1 免疫球蛋白（Ig）的情况下诱导 Th17 或 Treg 细胞，评估 PD-1/PD-L1 在 Th17/Treg 平衡中的作用。
部分胃切除术后，Treg 细胞百分比增加，Foxp3 和 TGF-β1 的表达升高（p<0.05），而 Th17 细胞百分比、RORγt 和 IL-17 的表达降低（p<0.05）。手术组的 PD-1 和 PD-L1 水平高于对照组和假手术组（p<0.05）。在体外，与同型组相比，抗 PD-1 治疗组 Th17 细胞的极化增强，而 Treg 细胞的极化受到抑制（p<0.05）。
部分胃切除术导致 Th17/Treg 失衡，并增加 PD-1 和 PD-L1 的表达。阻断 PD-1/PD-L1 通路可减轻胃手术引起的 Th17/Treg 细胞失衡。
