Upregulation of CCL20 and Recruitment of CCR6⁺Gastric Infiltrating Lymphocytes inHelicobacter pyloriGastritis

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 ␤-chemokine receptor for CCL20 (MIP-3␣/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-1␤ 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.

Chemokine receptors in gastric MALT lymphoma: loss of CXCR4 and upregulation of CXCR7 is associated with progression to diffuse large B-cell lymphoma

“…In H. pylori-associated gastritis, recruitment of T-and B cells, dendritic cells and neutrophil granulocytes is mediated by a variety of chemokines interacting with their cognate receptors such as CCR7, CCR5, CXCR1 and CXCR4 expressed on infiltrating immunological cells. 30,[36][37][38][39][40][41] Consistent with these findings, we also observed upregulated mRNA transcripts of CCR8, CCR9, CXCR3 and CXCR7.…”

Clinical manifestations and epigenetic mechanisms of gastric mucosa associated lymphoid tissue lymphoma and long‑term follow‑up following Helicobacter�pylori eradication

“…H. pylori colonization induces systemic and mucosal immune responses (24). Bacterial colonization of the gastric mucosa triggers lymphoid infiltration (25) and the formation of acquired MALTs. H. pylori infection induces and sustains an actively proliferating B-cell population via direct and indirect immunologic stimulation and infiltrating T cells serve an important role in the development of MALT lymphomas (24,26).…”

Interplay between Helicobacter pylori and immune cells in immune pathogenesis of gastric inflammation and mucosal pathology

“…6,[8][9][10] It has been demonstrated that T helper type 1 cells selectively increased during H. pylori infection. [11][12][13][14][15] T helper type 1 cytokines, such as gamma interferon (IFN-c) and tumor-necrosis factor alpha (TNF-a), can increase the release of proinflammatory cytokines, augmenting apoptosis induced by H. pylori. 10 H. pylori infection could also induce gastric mucosa damage by increasing expression of Fas in gastric epithelial cells, leading to gastric epithelial cell apoptosis through Fas/FasL interaction with infiltrating T cells.…”