Programmed death 1/programmed cell death-ligand 1 pathway participates in gastric surgery-induced imbalance of T-helper 17/regulatory T cells in mice.

J Trauma Acute Care Surg

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.

Published: September 2018

AI Article Synopsis

  • The balance between T-helper 17 (Th17) and regulatory T (Treg) cells is crucial for maintaining immune health, but the impact of gastric surgery on this balance is not well understood.
  • Mice underwent either partial gastrectomy or a sham procedure, and researchers measured changes in Treg and Th17 cell percentages and related cytokine levels over time.
  • Results indicated that gastric surgery increased Treg cells and associated factors while decreasing Th17 cells, with higher expressions of PD-1 and PD-L1, suggesting that blocking this pathway could help restore the Th17/Treg balance post-surgery.

Article Abstract

Background: 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.

Methods: 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.

Results: 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).

Conclusion: 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.

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http://dx.doi.org/10.1097/TA.0000000000001903DOI Listing

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