[Gut] A pro-inflammatory role for Th22 cells in Helicobacter pylori-associated gastritis [Th22细胞在幽门螺杆菌相关感染性胃炎中的促炎作用]

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Authors
Yuan Zhuang, Ping Cheng, Xiao-fei Liu, Liu-sheng Peng, Bo-sheng Li, Ting-ting Wang, Na Chen, Wen-hua Li, Yun Shi, Weisan Chen, Ken C Pang, Ming Zeng, Xu-hu Mao, Shi-ming Yang, Hong Guo, Gang Guo, Tao Liu, Qian-fei Zuo, Hui-jie Yang, Liu-yang Yang, Fang-yuan Mao, Yi-pin Lv, Quan-ming Zou

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.

Gut 2015;64:1368-1378 doi:10.1136/gutjnl-2014-307020