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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Actins / genetics
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Actins / immunology
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CD4-Positive T-Lymphocytes / drug effects
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CD4-Positive T-Lymphocytes / microbiology
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CD4-Positive T-Lymphocytes / pathology
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Cell Differentiation / drug effects
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Coculture Techniques
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Gastric Mucosa / drug effects
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Gastric Mucosa / microbiology
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Gastric Mucosa / pathology
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Gene Expression / drug effects
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Helicobacter Infections / immunology
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Helicobacter Infections / microbiology
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Helicobacter Infections / pathology*
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Helicobacter pylori / physiology*
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Histocompatibility Antigens Class II / genetics
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Histocompatibility Antigens Class II / immunology
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Humans
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Interleukin-6 / pharmacology
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Interleukins / pharmacology
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Myofibroblasts / drug effects
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Myofibroblasts / microbiology
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Myofibroblasts / pathology*
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Primary Cell Culture
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Signal Transduction / drug effects
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Stomach Neoplasms / immunology
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Stomach Neoplasms / microbiology
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Stomach Neoplasms / pathology*
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Stromal Cells / drug effects
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Stromal Cells / microbiology
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Stromal Cells / pathology*
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Th17 Cells / drug effects
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Th17 Cells / microbiology
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Th17 Cells / pathology*
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Thy-1 Antigens / genetics
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Thy-1 Antigens / immunology
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Transforming Growth Factor beta / pharmacology
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Tumor Microenvironment / immunology
Substances
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ACTA2 protein, human
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Actins
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Histocompatibility Antigens Class II
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IL6 protein, human
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Interleukin-6
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Interleukins
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Thy-1 Antigens
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Transforming Growth Factor beta
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interleukin-21