Stromal regulation of human gastric dendritic cells restricts the Th1 response to Helicobacter pylori.

Academic Article

Abstract

  • BACKGROUND & AIMS: Mucosal dendritic cells (DCs) play a key role in initiating the T-helper (Th)1 response to Helicobacter pylori. To further elucidate the mucosal response to H pylori, we examined whether gastric stromal factors condition DCs to support tolerance to H pylori, analogous to intestinal stromal factor-driven macrophage tolerance to commensal bacteria. METHODS: To model mucosal DC development, we isolated and cultured cell-depleted human stroma/extracellular matrix from fresh gastric and intestinal mucosa to generate stroma-conditioned media. We then analyzed the capacity of stroma-conditioned media-treated monocyte-derived DCs and primary human gastric and intestinal DCs pulsed in vitro with H pylori to induce T-cell proliferation and interferon gamma secretion. RESULTS: Stromal factors in gastric mucosa suppressed H pylori-stimulated DC activation and the ability of DCs to drive a Th1 proliferative and cytokine response to H pylori. The ability of gastric stromal factors to down-regulate DC function was similar to that of intestinal stromal factors and was independent of transforming growth factor β, prostaglandin E₂, interleukin (IL)-10, and thymic stromal lymphopoietin. Stroma-conditioned media-induced reduction in DC-stimulated Th1 responses was associated with reduced DC release of IL-12. CONCLUSIONS: Gastric stromal factors down-regulate DC responsiveness to H pylori, resulting in a dampened gastric Th1 response. We speculate that stroma-induced down-regulation of DC function contributes to the permissiveness of both gastric and intestinal mucosa to colonization by persistent residential microbes.
  • Published In

  • Gastroenterology  Journal
  • Keywords

  • Cell Communication, Cell Proliferation, Cells, Cultured, Chemokines, CXC, Culture Media, Conditioned, Cytokines, Dendritic Cells, Dinoprostone, Gastric Mucosa, Helicobacter pylori, Humans, Interleukin-10, Intestine, Small, Stomach, Stromal Cells, Th1 Cells, Transforming Growth Factor beta
  • Digital Object Identifier (doi)

    Author List

  • Bimczok D; Grams JM; Stahl RD; Waites KB; Smythies LE; Smith PD
  • Start Page

  • 929
  • End Page

  • 938
  • Volume

  • 141
  • Issue

  • 3