Publication Date:
2015-08-09
Description:
Objective 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. Design 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. Results 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. Conclusions 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.
Keywords:
Open access, Stomach and duodenum
Print ISSN:
0017-5749
Electronic ISSN:
1468-3288
Topics:
Medicine
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