title: Stromal regulation of human gastric dendritic cells restricts the Th1 response to Helicobacter pylori.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Medicine, Division of Gastroenterology and Hepatology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Diane
authors.initials: D
authors.lastname: Bimczok
authors.forename: Jayleen M
authors.initials: JM
authors.lastname: Grams
authors.forename: Richard D
authors.initials: RD
authors.lastname: Stahl
authors.forename: Ken B
authors.initials: KB
authors.lastname: Waites
authors.forename: Lesley E
authors.initials: LE
authors.lastname: Smythies
authors.forename: Phillip D
authors.initials: PD
authors.lastname: Smith
mesh_terms: D002450:Cell Communication / Q000502:physiology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D019743:Chemokines, CXC / Q000378:metabolism / Q000494:pharmacology; D017077:Culture Media, Conditioned / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism; D016480:Helicobacter pylori / Q000502:physiology*; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D007421:Intestine, Small / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D013270:Stomach / Q000166:cytology* / Q000187:drug effects; D017154:Stromal Cells / Q000166:cytology* / Q000378:metabolism; D018417:Th1 Cells / Q000166:cytology*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D019743:Chemokines, CXC; D017077:Culture Media, Conditioned; D016207:Cytokines; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D015232:Dinoprostone; D000094632:Thymic Stromal Lymphopoietin