PT  - JOURNAL ARTICLE
AU  - Zhuang, Yuan
AU  - Cheng, Ping
AU  - Liu, Xiao-fei
AU  - Peng, Liu-sheng
AU  - Li, Bo-sheng
AU  - Wang, Ting-ting
AU  - Chen, Na
AU  - Li, Wen-hua
AU  - Shi, Yun
AU  - Chen, Weisan
AU  - Pang, Ken C
AU  - Zeng, Ming
AU  - Mao, Xu-hu
AU  - Yang, Shi-ming
AU  - Guo, Hong
AU  - Guo, Gang
AU  - Liu, Tao
AU  - Zuo, Qian-fei
AU  - Yang, Hui-jie
AU  - Yang, Liu-yang
AU  - Mao, Fang-yuan
AU  - Lv, Yi-pin
AU  - Zou, Quan-ming
TI  - A pro-inflammatory role for Th22 cells in <em>Helicobacter pylori</em>-associated gastritis
AID  - 10.1136/gutjnl-2014-307020
DP  - 2015 Sep 01
TA  - Gut
PG  - 1368--1378
VI  - 64
IP  - 9
4099  - http://gut.bmj.com/content/64/9/1368.short
4100  - http://gut.bmj.com/content/64/9/1368.full
SO  - Gut2015 Sep 01; 64
AB  - 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.