Stromal regulation of human gastric dendritic cells restricts the Th1 response to Helicobacter pylori.
| Autor: | Bimczok D; Department of Medicine, Division of Gastroenterology and Hepatology, University of Alabama at Birmingham, Birmingham, Alabama, USA., Grams JM, Stahl RD, Waites KB, Smythies LE, Smith PD |
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| Jazyk: | angličtina |
| Zdroj: | Gastroenterology [Gastroenterology] 2011 Sep; Vol. 141 (3), pp. 929-38. Date of Electronic Publication: 2011 Jun 12. |
| DOI: | 10.1053/j.gastro.2011.06.006 |
| Abstrakt: | 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. (Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.) |
| Databáze: | MEDLINE |
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