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NAT MICROBIOL:生物物理所等解析调控肠道免疫炎症平衡的新机制

2017-04-19 佚名 生物物理研究所

由中国科学院生物物理研究所感染与免疫重点实验室果蝇研究团队完成的论文 Bap180/Baf180 is required to maintain homeostasis of intestinal innate immune response in Drosophila and mice 以 article 的形式,于 4 月 18 日发表在最新一期的《自然 - 微生物学》(Nature Micr


Bap180 维持肠道粘膜免疫稳态的分子机制示意图

由中国科学院生物物理研究所感染免疫重点实验室果蝇研究团队完成的论文 Bap180/Baf180 is required to maintain homeostasis of intestinal innate immune response in Drosophila and mice 以 article 的形式,于 4 月 18 日发表在最新一期的《自然 - 微生物学》(Nature Microbiology)杂志上。

肠道组织是机体最大的粘膜免疫场所,其中作为第一道防线的天然免疫对维持肠道免疫微环境平衡至关重要。其不仅要快速有力地清除入侵的病原菌,同时要维持共生菌。而过度活跃的天然免疫反应则会引起肠道微环境的紊乱以及肠上皮组织损伤,导致局部的肠炎疾病(Inflammatory Bowel Disease,IBD)的发生,甚至引发哮喘和 I 型糖尿病等机体系统性疾病。因此深入了解并掌握肠道天然免疫应答的平衡机理对于人类健康十分必要。

借助同高等动物高度类似的天然免疫信号通路和肠道结构,果蝇已被广泛应用于天然免疫,尤其是肠道粘膜免疫的研究。基于此,中科院感染与免疫重点实验室果蝇研究团队利用果蝇构建了成熟的病原菌感染模型,并利用大规模遗传筛选体系,寻找到 Bap180 因子具有调节肠道天然免疫平衡的新功能。在该研究中发现,Bap180 因子本身应答于肠道的天然免疫通路 IMD(同源于高等动物 NF-kB 通路),并以负反馈的方式在转录水平上限制 IMD 天然免疫通路的过度活化,同时抑制由促炎因子 Eiger(同源于高等动物 TNF)介导的肠道炎性风暴和肠上皮组织损伤。肠上皮特异敲除小鼠进一步证实了 Baf180(同源于果蝇 Bap180)在高等动物中具有同样的保守机制。不仅如此,该研究还表明 Bap180 因子不仅针对病原菌急性感染所造成的炎性风暴有抑制作用,同时对于共生菌所触发的肠道慢性炎症的积累也具有重要的平衡作用。因此,研究团队在该研究中发现了一个重要的监控机体肠道天然免疫平衡的调节因子 Bap180/Baf180,并解析了其可以作为关联天然免疫通路和炎性反应的关键节点,为今后肠炎诊断或是药物靶点的开发提供了重要的理论依据。

生物物理所为该研究工作第一单位,中科院感染与免疫重点实验室助理研究员贺晓萌和副研究员俞珺璟为论文共同第一作者,中科院感染与免疫重点实验室研究员潘磊和中科院上海巴斯德研究所研究员唐宏为论文的共同通讯作者。该研究受中科院青促会和国家自然科学基金委的共同资助。

原始出处:

Xiaomeng He, Junjing Yu, Min Wang,et al. Bap180/Baf180 is required to maintain homeostasis of intestinal innate immune response in Drosophila and mice. Nature Microbiology 2, Article number: 17056 (2017). doi:10.1038/nmicrobiol.2017.56

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    2017-10-21 sunylz
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    2017-08-25 hongbochen
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    2017-09-14 xjy02
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    2017-07-31 liye789132251

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