Role of Treg and TH17 cells of the gastric mucosa in children with Helicobacter pylori gastritis

J Pediatr Gastroenterol Nutr. 2014 Feb;58(2):245-51. doi: 10.1097/MPG.0000000000000194.

Abstract

Objective: The aim of the present study was to examine the expression of FOXP3, interleukin (IL)-10, transforming growth factor (TGF)-β1, IL-17A, and T helper 17 (TH17) cells/FOXP3+ regulatory T (Treg) cells balance in the gastric mucosa of children with Helicobacter pylori infection, in relation to the gastric histopathology.

Methods: Antral mucosal biopsies were obtained from 20 children with H pylori(+) gastritis and 20 age- and sex-matched normal controls. Histopathology was assessed by the updated Sydney classification. Gene expression of FOXP3, IL-10, and TGF-β1 was analyzed by quantitative real-time polymerase chain reaction. Immunohistochemical staining for FOXP3+ Treg and TH17 cells was performed.

Results: The gene expression levels of FOXP3, TGF-β1, and IL-10 messenger RNA (mRNA) and the number of FOXP3+ Treg were significantly higher in the H pylori(+) gastritis group than in the control group (P < 0.01). FOXP3 mRNA levels were correlated positively with TGF-β1 and IL-10 mRNA levels in the H pylori(+) gastritis group (P < 0.05). Furthermore, FOXP3 mRNA levels were correlated positively with the bacterial density, infiltration of polymorphonuclear cells, and mononuclear cells in the H pylori(+) gastritis group (P < 0.05). The number of TH17 cells was significantly higher in the H pylori(+) gastritis group than in the control group (P < 0.05). In addition, the number of TH17 cells was correlated negatively with the bacterial density and positively with the inflammatory scores of polymorphonuclear cells and mononuclear cells in the H pylori(+) gastritis group (P < 0.05). A negative correlation between the TH17 cells/FOXP3+ Treg ratio and the bacterial density was demonstrated in the H pylori(+) gastritis group (P < 0.05).

Conclusions: This study suggested that a TH17/Treg balance toward a Treg-biased response favors the persistence of bacteria, causing chronic active gastritis.

MeSH terms

  • Adolescent
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Female
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / metabolism
  • Gastric Mucosa / immunology*
  • Gastric Mucosa / metabolism
  • Gastric Mucosa / microbiology
  • Gastric Mucosa / pathology
  • Gastritis / immunology*
  • Gastritis / metabolism
  • Gastritis / microbiology
  • Gastritis / pathology
  • Helicobacter Infections / immunology*
  • Helicobacter Infections / metabolism
  • Helicobacter Infections / microbiology
  • Helicobacter Infections / pathology
  • Helicobacter pylori / growth & development*
  • Humans
  • Inflammation / metabolism
  • Interleukin-10 / genetics
  • Interleukin-10 / metabolism
  • Interleukin-17 / metabolism
  • Leukocytes, Mononuclear / metabolism
  • Male
  • RNA, Messenger / metabolism
  • T-Lymphocytes, Regulatory / metabolism*
  • Th17 Cells / metabolism*
  • Transforming Growth Factor beta1 / genetics
  • Transforming Growth Factor beta1 / metabolism

Substances

  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Interleukin-17
  • RNA, Messenger
  • Transforming Growth Factor beta1
  • Interleukin-10