A pro-inflammatory role for Th22 cells in Helicobacter pylori-associated gastritis Academic Article uri icon

abstract

  • Helper T (Th) cell responses are critical for the pathogenesis of Helicobacter pylori-induced gastritis. Th22 cells represent a newly discovered Th cell subset, but their relevance to H. pylori-induced gastritis is unknown.Flow cytometry, real-time PCR and ELISA analyses were performed to examine cell, protein and transcript levels in gastric samples from patients and mice infected with H. pylori. Gastric tissues from interleukin (IL)-22-deficient and wild-type (control) mice were also examined. Tissue inflammation was determined for pro-inflammatory cell infiltration and pro-inflammatory protein production. Gastric epithelial cells and myeloid-derived suppressor cells (MDSC) were isolated, stimulated and/or cultured for Th22 cell function assays.Th22 cells accumulated in gastric mucosa of both patients and mice infected with H. pylori. Th22 cell polarisation was promoted via the production of IL-23 by dendritic cells (DC) during H. pylori infection, and resulted in increased inflammation within the gastric mucosa. This inflammation was characterised by the CXCR2-dependent influx of MDSCs, whose migration was induced via the IL-22-dependent production of CXCL2 by gastric epithelial cells. Under the influence of IL-22, MDSCs, in turn, produced pro-inflammatory proteins, such as S100A8 and S100A9, and suppressed Th1 cell responses, thereby contributing to the development of H. pylori-associated gastritis.This study, therefore, identifies a novel regulatory network involving H. pylori, DCs, Th22 cells, gastric epithelial cells and MDSCs, which collectively exert a pro-inflammatory effect within the gastric microenvironment. Efforts to inhibit this Th22-dependent pathway may therefore prove a valuable strategy in the therapy of H. pylori-associated gastritis.

authors

  • Zhuang, Y
  • Cheng, P
  • Liu, X-F
  • Peng, L-S
  • Li, B-S
  • Wang, T-T
  • Chen, N
  • Li, W-H
  • Shi, Y
  • Chen, W
  • Pang, KC
  • Zeng, M
  • Mao, X-H
  • Yang, S-M
  • Guo, H
  • Guo, G
  • Liu, T
  • Zuo, Q-F
  • Yang, H-J
  • Yang, L-Y
  • Mao, F-Y
  • Lv, Y-P
  • Zou, Q-M

publication date

  • 2015

has subject area

published in

  • Gut  Journal