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昼夜节律可影响先天免疫细胞与肠道稳态
2019-09-19 15:30

葡萄牙尚帕利莫未知问题研究中心的Henrique Veiga-Fernandes小组近日取得一项新成果。他们的研究显示,光线和大脑调节的生物钟回路调控3型先天淋巴细胞(ILC3)与肠道稳态。 2019年9月18日,国际知名学术期刊《自然》在线发表了这一成果。

研究人员发现,光线和大脑调控的昼夜节律回路调节小鼠的肠道ILC3、肠内稳态、肠道防御和宿主脂质代谢。研究人员发现肠道ILC3表现出时钟基因和ILC3相关转录因子的昼夜节律表达。ICL3中昼夜节律调节蛋白Arnt1的自主消失导致肠道ILC3稳态中断、上皮反应性受损、微生物群失调、肠道感染易感性增加以及脂质代谢受损。ILC3本身的Arnt1基因的缺失改变了ILC3的肠道“邮编受体”。值得注意的是,明暗循环、进食节律和微生物信号差异性调节ILC3时钟,而光信号是ILC3的主要影响因素。因此,手术或遗传诱导的脑节律性失调导致ILC3的昼夜节律振荡、微生物组失调和脂质代谢改变。这项工作揭示了一个昼夜节律回路,将环境光信号用于调节肠道ILC3、塑造肠道健康、新陈代谢和生物体内稳态。

据介绍,ILC3是炎症、感染、微生物群组成和代谢的主要调节者。ILC3和神经元细胞在不同粘膜位置相互作用以引导粘膜防御。然而,尚不清楚神经免疫回路是否在生物体水平上运作,来整合外在环境信号以协调ILC3反应。

附:英文原文

Title: Light-entrained and brain-tuned circadian circuits regulate ILC3s and gut homeostasis

Author: Cristina Godinho-Silva, Rita G. Domingues, Miguel Rendas, Bruno Raposo, Hlder Ribeiro, Joaquim Alves da Silva, Ana Vieira, Rui M. Costa, Nuno L. Barbosa-Morais, Tnia Carvalho, Henrique Veiga-Fernandes

Issue&Volume: 2019-09-18

Abstract: 

Group 3 innate lymphoid cells (ILC3s) are major regulators of inflammation, infection, microbiota composition and metabolism1. ILC3s and neuronal cells have been shown to interact at discrete mucosal locations to steer mucosal defence2,3. Nevertheless, it is unclear whether neuroimmune circuits operate at an organismal level, integrating extrinsic environmental signals to orchestrate ILC3 responses. Here we show that light-entrained and brain-tuned circadian circuits regulate enteric ILC3s, intestinal homeostasis, gut defence and host lipid metabolism in mice. We found that enteric ILC3s display circadian expression of clock genes and ILC3-related transcription factors. ILC3-autonomous ablation of the circadian regulator Arntl led to disrupted gut ILC3 homeostasis, impaired epithelial reactivity, a deregulated microbiome, increased susceptibility to bowel infection and disrupted lipid metabolism. Loss of ILC3-intrinsic Arntl shaped the gut ‘postcode receptors’ of ILC3s. Strikingly, light–dark cycles, feeding rhythms and microbial cues differentially regulated ILC3 clocks, with light signals being the major entraining cues of ILC3s. Accordingly, surgically or genetically induced deregulation of brain rhythmicity led to disrupted circadian ILC3 oscillations, a deregulated microbiome and altered lipid metabolism. Our work reveals a circadian circuitry that translates environmental light cues into enteric ILC3s, shaping intestinal health, metabolism and organismal homeostasis.

DOI: 10.1038/s41586-019-1579-3

Source:https://www.nature.com/articles/s41586-019-1579-3

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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