Stromal Regulation of Human Gastric Dendritic Cells Restricts the Th1 Response to Helicobacter pylori
Stromal Regulation of Human Gastric Dendritic Cells Restricts the Th1 Response to Helicobacter pylori
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DOI：
10.1053/j.gastro.2011.06.006
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发表时间：
2011-09-01
期刊：
影响因子：
29.4
通讯作者：
Smith, Phillip D.
中科院分区：
文献类型：
--
作者：
Bimczok, Diane;Grams, Jayleen M.;Smith, Phillip D.
背景与目的：粘膜树突状细胞(DCs)在启动幽门螺杆菌(Hp)诱导的辅助性T细胞(Th)1应答中起关键作用。为了进一步阐明粘膜对幽门螺杆菌的反应，我们研究了胃基质因子是否影响DC对幽门螺杆菌的耐受，类似于肠道基质因子驱动的巨噬细胞对共生菌的耐受。方法：从新鲜的胃和肠粘膜中分离和培养去细胞的人基质/细胞外基质，以产生基质条件培养液，以模拟粘膜DC的发育。然后，我们分析了基质条件培养液处理的单核细胞来源的DC和原代培养的人胃和肠树突状细胞在幽门螺杆菌刺激下诱导T细胞增殖和干扰素γ分泌的能力。结果：胃粘膜基质因子抑制了幽门螺杆菌刺激的DC的活化，抑制了DC对幽门螺杆菌刺激的Th1增殖和细胞因子反应。胃基质因子下调DC功能的能力与肠道基质因子相似，不依赖于转化生长因子β、前列腺素E_2、白介素10和胸腺基质淋巴生成素。基质条件培养液诱导DC刺激的Th1反应的减少与DC释放IL-12的减少有关。结论：胃基质因子下调DC对幽门螺杆菌的反应性，导致胃Th1反应减弱。我们推测，基质诱导的DC功能下调有助于胃和肠粘膜对持久栖息微生物的定植。
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 beta, 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.