Stromal cells induce Th17 during Helicobacter pylori infection and in the gastric tumor microenvironment.

Stromal cells induce Th17 during Helicobacter pylori infection and in the gastric tumor microenvironment.
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DOI:
10.1371/journal.pone.0053798
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Beswick EJ
Beswick EJ
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Pinchuk IV;Morris KT;Nofchissey RA;Earley RB;Wu JY;Ma TY;Beswick EJ

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胃癌与慢性炎症和幽门螺杆菌感染有关。 Th17 细胞是与感染和炎症相关的 CD4+ T 细胞;但它们在致癌过程中的作用和诱导机制尚不清楚。胃肌成纤维细胞/成纤维细胞 (GMF) 是丰富的 II 类 MHC 表达细胞,可充当新型抗原呈递细胞。在这里,我们证明了 Th17 在幽门螺杆菌感染的人体组织和胃肿瘤微环境中的积累。从人胃癌和幽门螺杆菌感染组织中分离的 GMF 与 CD4+ T 细胞共培养,以 IL-6、TGF-β 和 IL-21 依赖性方式诱导比正常组织中的 GMF 显着更高水平的 Th17。 Th17 需要与 GMF 上的 II 类 MHC 相互作用才能激活和增殖。这些研究表明,Th17 在幽门螺杆菌感染和胃癌期间在胃间质的炎症环境中被诱导,并且可能是炎症和癌发生之间的重要联系。
Gastric cancer is associated with chronic inflammation and Helicobacter pylori infection. Th17 cells are CD4+ T cells associated with infections and inflammation; but their role and mechanism of induction during carcinogenesis is not understood. Gastric myofibroblasts/fibroblasts (GMF) are abundant class II MHC expressing cells that act as novel antigen presenting cells. Here we have demonstrated the accumulation of Th17 in H. pylori-infected human tissues and in the gastric tumor microenvironment. GMF isolated from human gastric cancer and H. pylori infected tissues co-cultured with CD4+ T cells induced substantially higher levels of Th17 than GMF from normal tissues in an IL-6, TGF-β, and IL-21 dependent manner. Th17 required interaction with class II MHC on GMF for activation and proliferation. These studies suggest that Th17 are induced during both H. pylori infection and gastric cancer in the inflammatory milieu of gastric stroma and may be an important link between inflammation and carcinogenesis.
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