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Helicobacter pylori
Original article
A pro-inflammatory role for Th22 cells in Helicobacter pylori-associated gastritis
  1. Yuan Zhuang1,
  2. Ping Cheng1,
  3. Xiao-fei Liu1,2,
  4. Liu-sheng Peng1,
  5. Bo-sheng Li1,
  6. Ting-ting Wang1,
  7. Na Chen1,
  8. Wen-hua Li1,
  9. Yun Shi1,
  10. Weisan Chen3,
  11. Ken C Pang4,5,
  12. Ming Zeng6,
  13. Xu-hu Mao1,
  14. Shi-ming Yang7,
  15. Hong Guo7,
  16. Gang Guo1,
  17. Tao Liu1,
  18. Qian-fei Zuo1,
  19. Hui-jie Yang1,
  20. Liu-yang Yang1,
  21. Fang-yuan Mao1,
  22. Yi-pin Lv1,
  23. Quan-ming Zou1
  1. 1Department of Microbiology and Biochemical Pharmacy, National Engineering Research Centre of Immunological Products, College of Pharmacy, Third Military Medical University, Chongqing, China
  2. 2Department of Laboratory Medicine, General Hospital of Ji'nan Military Region of PLA, Ji'nan, Shandong, China
  3. 3School of Molecular Science, La Trobe University, Bundoora, Victoria, Australia
  4. 4Inflammation Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia
  5. 5Department of Paediatrics, The University of Melbourne, Parkville, Victoria, Australia
  6. 6National Institutes for Food and Drug Control, Beijing, China
  7. 7Department of Gastroenterology, XinQiao Hospital, Third Military Medical University, Chongqing, China
  1. Corresponding to Dr Yuan Zhuang, Department of Microbiology and Biochemical Pharmacy, National Engineering Research Centre of Immunological Products, College of Pharmacy, Third Military Medical University, No.30 Gaotanyan Street, Chongqing 400038, China; yuanzhuang1983{at}yahoo.com and Professor Quan-ming Zou, Department of Microbiology and Biochemical Pharmacy, National Engineering Research Centre of Immunological Products, College of Pharmacy, Third Military Medical University, No.30 Gaotanyan Street, Chongqing 400038, China; qmzou@tmmu.edu.cn

Abstract

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.

  • HELICOBACTER PYLORI
  • GASTRITIS

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 3.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/3.0/

https://doi.org/10.1136/gutjnl-2014-307020

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