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

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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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