A pro-inflammatory role for Th22 cells in Helicobacter pylori-associated gastritis

Zhuang, Y; Cheng, P; Liu, XF; Peng, LS; Li, BS; Wang, TT; Chen, N; Li, WH; Shi, Y; Chen, W; Pang, KC; Zeng, M; Mao, XH; Yang, SM; Guo, H; Guo, G; Liu, T; Zuo, QF; Yang, HJ; Yang, LY; Mao, FY; Lv, YP; Zou, QM

Author(s): Zhuang, Y; Cheng, P; Liu, XF; Peng, LS; Li, BS; Wang, TT; Chen, N; Li, WH; Shi, Y; Chen, W; Pang, KC; Zeng, M; Mao, XH; Yang, SM; Guo, H; Guo, G; Liu, T; Zuo, QF; Yang, HJ; Yang, LY; Mao, FY; Lv, YP; Zou, QM;
Details: Publication Year 2015-09,Volume 64,Issue #9,Page 1368-78
Journal Title: Gut
Publication Type: Journal Article
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.
Publisher: BMJ
Research Division(s): Inflammation
PubMed ID: 25134787
Link To PubMed Central Version: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4552937/
Publisher's Version: https://doi.org/10.1136/gutjnl-2014-307020
Open Access at Publisher's Site: http://gut.bmj.com/content/early/2014/08/18/gutjnl-2014-307020.long
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2014-09-12 02:01:48

Last Modified: 2015-10-30 08:32:52