对AHR信号的反控制调节肠道免疫力
Chris Schiering1, Emma Wincent2, Amina Metidji1
1The Francis Crick Institute, London, UK.
Nature
|February 2, 2017
概括
由于过度的CYP1A1酶活性,失调的烯受体 (AHR) 信号消耗了天然的AHR配体,损害了肠道免疫力. 饮食中的AHR配体可以恢复免疫功能,突出表皮细胞
科学领域:
- 免疫学
- 分子生物学
- 胃肠病学
背景情况:
- 基碳化合物受体 (AHR) 对于保持粘膜表面的平衡至关重要.
- 激活AHR会诱导细胞染色体P4501 (CYP1) 酶,这些酶会对AHR配体进行代谢以进行解毒.
- CYP1酶在调节体内AHR配体可用性的作用尚不清楚.
研究的目的:
- 调查CYP1酶是否调节了AHR配体的可用性.
- 确定失调的CYP1A1表达对小鼠的AHR信号和免疫功能的影响.
主要方法:
- 产生失调Cyp1a1表达的小鼠 (构成或局限于肠上皮细胞).
- 评估AHR连体水平,依赖AHR的免疫细胞群 (ILC3,Th17) 和对肠道感染的易感性.
- 通过饮食补充AHR连接剂的效果评估.
主要成果:
- 失调的Cyp1a1表达减少了天然的AHR连接体,形成了准AHR缺陷状态.
- 构成性Cyp1a1表达导致了依赖于AHR的ILC3和Th17细胞的丧失,并增加了对肠道感染的敏感性.
- 通过饮食摄入更多的AHR配体,抵消了过度配体降解的负面影响.
结论:
- 肠上皮细胞作为AHR连体供应的守门人.
- 通过CYP1酶进行反控制对于调节AHR通路的激活至关重要.
- 维持足够的AHR连接剂可用性对于肠道免疫平衡至关重要.
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