Upregulation of CCL20 and recruitment of CCR6+ gastric infiltrating lymphocytes in Helicobacter pylori gastritis

Infect Immun. 2007 Sep;75(9):4357-63. doi: 10.1128/IAI.01660-06. Epub 2007 Jun 11.

Abstract

Helicobacter pylori infection is associated with an inflammatory response in the gastric mucosa, leading to chronic gastritis, peptic ulcers, and gastric cancer. There is increased T-cell infiltration at the site of infection with H. pylori. CCR6, a specific beta-chemokine receptor for CCL20 (MIP-3alpha/LARC/exodus), has recently been reported to mediate lymphocyte homeostasis and immune responses in mucosal tissue, and it may play a role in chemokine-mediated lymphocyte trafficking during gastric inflammation. In this study, we investigated the role of CCR6 and its ligand, CCL20, in inducing an inflammatory response in the gastric mucosa during H. pylori infection. Gastric infiltrating T lymphocytes were isolated from endoscopic biopsy specimens of H. pylori gastritis patients and analyzed for the expression of the CCR6 chemokine receptor. Our results demonstrated that there was significantly increased CCR6 expression in CD3(+) T cells infiltrating the gastric mucosa, and the CCR6 ligand, the CCL20 chemokine, was selectively expressed in inflamed gastric tissues. The production of CCL20 was upregulated in response to H. pylori in gastric epithelial cells when there was stimulation by the proinflammatory cytokines interleukin-1beta and tumor necrosis factor alpha. Furthermore, recombinant CCL20 induced lymphocyte chemotaxis migration in fresh gastric T cells ex vivo, indicating that the gastric T cells could migrate toward inflammatory sites via CCR6/CCL20 interaction. Our results suggest that the interaction between CCL20 and CCR6 may play a role in chemokine-mediated lymphocyte trafficking during gastric inflammation in Helicobacter infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cells, Cultured
  • Chemokine CCL20
  • Chemokines, CC / biosynthesis*
  • Chemokines, CC / genetics
  • Chemotaxis, Leukocyte / genetics
  • Chemotaxis, Leukocyte / immunology*
  • Chronic Disease
  • Gastritis / immunology*
  • Gastritis / microbiology
  • Gastritis / pathology
  • Helicobacter Infections / immunology*
  • Helicobacter Infections / microbiology
  • Helicobacter Infections / pathology
  • Helicobacter pylori / immunology*
  • Humans
  • Immunologic Memory / genetics
  • Inflammation Mediators / metabolism
  • Inflammation Mediators / physiology
  • Lymphocyte Activation / genetics
  • Lymphocyte Activation / immunology
  • Macrophage Inflammatory Proteins / biosynthesis*
  • Macrophage Inflammatory Proteins / genetics
  • Receptors, CCR5 / biosynthesis
  • Receptors, CCR5 / genetics
  • Receptors, CCR6
  • Receptors, CXCR3
  • Receptors, Chemokine / biosynthesis*
  • Receptors, Chemokine / genetics
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocyte Subsets / pathology
  • Th1 Cells / immunology
  • Th1 Cells / metabolism
  • Th1 Cells / pathology
  • Up-Regulation / immunology*

Substances

  • CCL20 protein, human
  • CCR6 protein, human
  • CXCR3 protein, human
  • Chemokine CCL20
  • Chemokines, CC
  • Inflammation Mediators
  • Macrophage Inflammatory Proteins
  • Receptors, CCR5
  • Receptors, CCR6
  • Receptors, CXCR3
  • Receptors, Chemokine