title: A pro-inflammatory role for Th22 cells in Helicobacter pylori-associated gastritis.
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.
  
  
  METHODS
  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.
authors.affiliation: Department of Microbiology and Biochemical Pharmacy, National Engineering Research Centre of Immunological Products, College of Pharmacy, Third Military Medical University, Chongqing, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhuang
authors.affiliation: Department of Microbiology and Biochemical Pharmacy, National Engineering Research Centre of Immunological Products, College of Pharmacy, Third Military Medical University, Chongqing, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Cheng
authors.affiliation: Department of Microbiology and Biochemical Pharmacy, National Engineering Research Centre of Immunological Products, College of Pharmacy, Third Military Medical University, Chongqing, China Department of Laboratory Medicine, General Hospital of Ji'nan Military Region of PLA, Ji'nan, Shandong, China.
authors.forename: Xiao-fei
authors.initials: XF
authors.lastname: Liu
authors.affiliation: Department of Microbiology and Biochemical Pharmacy, National Engineering Research Centre of Immunological Products, College of Pharmacy, Third Military Medical University, Chongqing, China.
authors.forename: Liu-sheng
authors.initials: LS
authors.lastname: Peng
authors.affiliation: Department of Microbiology and Biochemical Pharmacy, National Engineering Research Centre of Immunological Products, College of Pharmacy, Third Military Medical University, Chongqing, China.
authors.forename: Bo-sheng
authors.initials: BS
authors.lastname: Li
authors.affiliation: Department of Microbiology and Biochemical Pharmacy, National Engineering Research Centre of Immunological Products, College of Pharmacy, Third Military Medical University, Chongqing, China.
authors.forename: Ting-ting
authors.initials: TT
authors.lastname: Wang
authors.affiliation: Department of Microbiology and Biochemical Pharmacy, National Engineering Research Centre of Immunological Products, College of Pharmacy, Third Military Medical University, Chongqing, China.
authors.forename: Na
authors.initials: N
authors.lastname: Chen
authors.affiliation: Department of Microbiology and Biochemical Pharmacy, National Engineering Research Centre of Immunological Products, College of Pharmacy, Third Military Medical University, Chongqing, China.
authors.forename: Wen-hua
authors.initials: WH
authors.lastname: Li
authors.affiliation: Department of Microbiology and Biochemical Pharmacy, National Engineering Research Centre of Immunological Products, College of Pharmacy, Third Military Medical University, Chongqing, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Shi
authors.affiliation: School of Molecular Science, La Trobe University, Bundoora, Victoria, Australia.
authors.forename: Weisan
authors.initials: W
authors.lastname: Chen
authors.affiliation: Inflammation Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia Department of Paediatrics, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Ken C
authors.initials: KC
authors.lastname: Pang
authors.affiliation: National Institutes for Food and Drug Control, Beijing, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Zeng
authors.affiliation: Department of Microbiology and Biochemical Pharmacy, National Engineering Research Centre of Immunological Products, College of Pharmacy, Third Military Medical University, Chongqing, China.
authors.forename: Xu-hu
authors.initials: XH
authors.lastname: Mao
authors.affiliation: Department of Gastroenterology, XinQiao Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Shi-ming
authors.initials: SM
authors.lastname: Yang
authors.affiliation: Department of Gastroenterology, XinQiao Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Guo
authors.affiliation: Department of Microbiology and Biochemical Pharmacy, National Engineering Research Centre of Immunological Products, College of Pharmacy, Third Military Medical University, Chongqing, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Guo
authors.affiliation: Department of Microbiology and Biochemical Pharmacy, National Engineering Research Centre of Immunological Products, College of Pharmacy, Third Military Medical University, Chongqing, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Microbiology and Biochemical Pharmacy, National Engineering Research Centre of Immunological Products, College of Pharmacy, Third Military Medical University, Chongqing, China.
authors.forename: Qian-fei
authors.initials: QF
authors.lastname: Zuo
authors.affiliation: Department of Microbiology and Biochemical Pharmacy, National Engineering Research Centre of Immunological Products, College of Pharmacy, Third Military Medical University, Chongqing, China.
authors.forename: Hui-jie
authors.initials: HJ
authors.lastname: Yang
authors.affiliation: Department of Microbiology and Biochemical Pharmacy, National Engineering Research Centre of Immunological Products, College of Pharmacy, Third Military Medical University, Chongqing, China.
authors.forename: Liu-yang
authors.initials: LY
authors.lastname: Yang
authors.affiliation: Department of Microbiology and Biochemical Pharmacy, National Engineering Research Centre of Immunological Products, College of Pharmacy, Third Military Medical University, Chongqing, China.
authors.forename: Fang-yuan
authors.initials: FY
authors.lastname: Mao
authors.affiliation: Department of Microbiology and Biochemical Pharmacy, National Engineering Research Centre of Immunological Products, College of Pharmacy, Third Military Medical University, Chongqing, China.
authors.forename: Yi-pin
authors.initials: YP
authors.lastname: Lv
authors.affiliation: Department of Microbiology and Biochemical Pharmacy, National Engineering Research Centre of Immunological Products, College of Pharmacy, Third Military Medical University, Chongqing, China.
authors.forename: Quan-ming
authors.initials: QM
authors.lastname: Zou
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002478:Cells, Cultured; D054426:Chemokine CXCL2 / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism; D005260:Female; D005756:Gastritis / Q000276:immunology / Q000382:microbiology* / Q000503:physiopathology; D016481:Helicobacter Infections / Q000276:immunology* / Q000503:physiopathology; D016480:Helicobacter pylori / Q000276:immunology* / Q000472:pathogenicity; D006801:Humans; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism*; D007378:Interleukins / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011897:Random Allocation; D060888:Real-Time Polymerase Chain Reaction; D012380:Role; D012680:Sensitivity and Specificity; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism; D014162:Transfection; D000097043:Interleukin-22
chemical_list: D015415:Biomarkers; D054426:Chemokine CXCL2; D018836:Inflammation Mediators; D007378:Interleukins; D000097043:Interleukin-22
keywords: GASTRITIS; HELICOBACTER PYLORI