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病毒加敏感性基因相互作用决定克罗恩病基因在肠道中的Atg16L1表型
Ken Cadwell1, Khushbu K Patel, Nicole S Maloney
1Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Cell
|July 7, 2010
概括
一种特定的病毒感染与克罗恩病基因突变相互作用,引发小鼠的肠道问题. 这凸显了基因变异,病毒和肠道细菌如何导致炎症疾病表型.
科学领域:
- 胃肠病学 胃肠病学
- 免疫学 免疫学 免疫学
- 微生物学 微生物学
背景情况:
- 对于炎症性疾病的常见遗传风险等位基因尚未完全理解.
- 只有很小一部分具有这些等位基因的个体会患上疾病.
研究的目的:
- 对携带遗传风险因素的个体疾病发展背后的分子机制进行研究.
- 阐明病毒敏感性基因相互作用在炎症性肠病病原发生中的作用.
主要方法:
- 通过特定的病毒感染和克罗恩氏病易感基因突变 (Atg16L1) 诱导小鼠的肠道病理.
- 分析帕内斯细胞功能,基因表达模式,以及对硫酸诱导的损伤的反应.
- 评估TNF-alpha,IFN-gamma和开始性细菌在疾病发展中的作用.
主要成果:
- 病毒敏感性基因相互作用导致异常的颗粒包装,并改变了帕内斯细胞中的基因表达.
- 这种相互作用导致化学损伤后类似克罗恩病的病理.
- 病理依赖于TNF-alpha和IFN-gamma信号传递,并通过宽谱抗生素减轻.
结论:
- 与Atg16L1基因突变相互作用的特定病毒感染可以在小鼠中诱导类似克罗恩氏病的肠道病理.
- 遗传敏感个体的炎症性疾病表型可能来自病毒感染,宿主遗传和包括微生物组在内的环境因素的复杂相互作用.
- 这些发现提供了遗传倾向,病毒触发因素和炎症性肠道疾病发展之间的机制联系.
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