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Isolation and Th17 Differentiation of Naïve CD4 T Lymphocytes
Published on: September 26, 2013
与腺瘤相关的屏障缺陷和微生物产品驱动IL-23/IL-17介导的瘤生长
Sergei I Grivennikov1, Kepeng Wang, Daniel Mucida
1Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California, San Diego, La Jolla, California 92093-0723, USA.
Nature
|October 5, 2012
概括
结肠直肠癌的生长是由炎症驱动的. 瘤中的遗传变化允许微生物产品进入,引发炎症,促进瘤进展,即使没有炎症性肠病.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 胃肠病学 胃肠病学
背景情况:
- 结肠直肠癌 (CRC) 经常在没有炎症性肠病的情况下发展,但却表现出炎症性基因特征并透.
- 瘤引起的炎症,特别是涉及T-辅助干白素-17 (T(H) 17) 细胞,与CRC存活率低下有关.
- 驱动CRC中瘤引起的炎症的机制尚不清楚.
研究的目的:
- 研究驱动结直肠癌中瘤引起的炎症的机制.
- 阐明白细胞细胞瘤发育中白细胞蛋白-23 (IL-23) 和白细胞蛋白-17 (IL-17) 的作用.
- 探索上皮质屏障完整性对CRC发展的影响.
主要方法:
- 利用大肠直肠瘤发生的小鼠模型.
- 分析基因表达,包括炎症特征和屏障蛋白.
- 研究了IL-23/IL-17信号通路的作用.
- 检查了免疫细胞透及其激活.
主要成果:
- IL-23信号显著促进CRC生长,进展和瘤IL-17反应的发展.
- 瘤相关的髓状细胞,被瘤透的微生物产品激活,是IL-23的主要来源.
- 在早期和晚期结直肠瘤中观察到屏障蛋白的缺陷表达,促进微生物入侵.
结论:
- 由致癌的遗传病变引起的上皮屏障恶化,使微生物产品能够入侵瘤.
- 这种入侵触发了由IL-23和IL-17介导的瘤引起的炎症,随后推动了瘤的生长和进展.
- 了解这些机制为CRC提供了潜在的治疗点.
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