IL-23-mediated regulation of IL-17 production in Helicobacter pylori-infected gastric mucosa

Roberta Caruso, Daniele Fina, Omer Alessandro Paoluzi, Giovanna Del Vecchio Blanco, Carmine Stolfi, Angelamaria Rizzo, Flavio Caprioli, Massimiliano Sarra, Fabio Andrei, Massimo Claudio Fantini, Thomas T. MacDonald, Francesco Pallone, Giovanni Monteleone

Research output: Contribution to journalArticlepeer-review

Abstract

Helicobacter pylori (Hp) infection is associated with a marked infiltration of the gastric mucosa by inflammatory cells. The molecular pathways that control Hp-associated inflammatory reaction are complex, but locally induced cytokines seem to contribute to maintaining the ongoing inflammation. We have previously shown that IL-17 is over-produced in Hp-infected gastric mucosa, and that IL-17 stimulates the synthesis of IL-8, the major neutrophil chemoattractant. Factors/ mechanisms that regulate IL-17 expression remain, however, unknown. In this study, we initially expanded our previous data, showing that CD4± and CD8± T cells are a source of IL-17 in Hp-infected samples. Since IL-23 enhances T cell-derived IL-17 during bacterial infections, we then assessed the role of IL-23 in controlling IL-17 expression in Hp-colonized stomach. Using real-time PCR and ELISA, IL-23 was detected in all gastric biopsies, but its expression was more pronounced in Hp-infected samples in comparison to controls. Treatment of normal gastric lamina propria mononuclear cells (LPMC) with IL-23 enhanced Stat3 activation and IL-17 secretion, and pharmacological inhibition of Stat3 prevented IL-23-driven IL-17 synthesis. Consistently, blockade of IL-23 in cultures of LPMC from Hp-infected patients reduced Stat3 activation and IL-17 production. Data show that IL-23 is overexpressed in Hp-infected gastric mucosa where it could contribute to sustaining IL-17 production.

Original languageEnglish
Pages (from-to)470-478
Number of pages9
JournalEuropean Journal of Immunology
Volume38
Issue number2
DOIs
Publication statusPublished - Feb 2008

Keywords

  • Helicobater pylori
  • IL-17
  • IL-23

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

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