Stromal cells induce Th17 during Helicobacter pylori infection and in the gastric tumor microenvironment. Academic Article uri icon

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abstract

  • Gastric cancer is associated with chronic inflammation and Helicobacter pylori infection. Th17 cells are CD4(+) T cells associated with infections and inflammation; but their role and mechanism of induction during carcinogenesis is not understood. Gastric myofibroblasts/fibroblasts (GMF) are abundant class II MHC expressing cells that act as novel antigen presenting cells. Here we have demonstrated the accumulation of Th17 in H. pylori-infected human tissues and in the gastric tumor microenvironment. GMF isolated from human gastric cancer and H. pylori infected tissues co-cultured with CD4(+) T cells induced substantially higher levels of Th17 than GMF from normal tissues in an IL-6, TGF-β, and IL-21 dependent manner. Th17 required interaction with class II MHC on GMF for activation and proliferation. These studies suggest that Th17 are induced during both H. pylori infection and gastric cancer in the inflammatory milieu of gastric stroma and may be an important link between inflammation and carcinogenesis.

date/time value

  • 2013

Digital Object Identifier (DOI)

  • 10.1371/journal.pone.0053798

PubMed Identifier

  • 23365642

volume

  • 8

number

  • 1

keywords

  • Actins
  • Antigens, Thy-1
  • CD4-Positive T-Lymphocytes
  • Cell Differentiation
  • Coculture Techniques
  • Gastric Mucosa
  • Gene Expression
  • Helicobacter Infections
  • Helicobacter pylori
  • Histocompatibility Antigens Class II
  • Humans
  • Interleukin-6
  • Interleukins
  • Myofibroblasts
  • Primary Cell Culture
  • Signal Transduction
  • Stomach Neoplasms
  • Stromal Cells
  • Th17 Cells
  • Transforming Growth Factor beta
  • Tumor Microenvironment