喂食依赖性VIP神经元与ILC3之间的回路调节肠道屏障
2020-02-14   阅读:489   来源:自然

美国纽约大学医学院Dan R. Littman研究小组发现,喂食依赖性VIP神经元与ILC3之间的回路调节肠道屏障。该项研究成果2020年2月12日在线发表在《自然》上。

研究人员报道了食物摄入触发的肠道神经元信号如何与由3型先天性淋巴样细胞(ILC3)控制的肠道抗菌和代谢反应进行整合。食物摄取会迅速激活表达血管活性肠肽(VIP)的肠道神经元。固有层中产生VIP的神经元(VIPergic神经元)的投影非常接近选择性表达2型VIP受体(VIPR2或VPAC2)的ILC3。ILCR3产生的IL-22(被共生的微生物所上调,如节段性丝状细菌SFB)被VIPR2所抑制。因此,上皮细胞产生的抗菌肽减少,但脂质结合蛋白和转运蛋白的表达增加。在食物摄取期间,VIPergic神经元的激活增强了上皮相关SFB的生长并增加了脂质吸收。这些研究结果揭示了一种喂食和昼夜调节的动态肠道神经免疫回路,其可促进IL-22介导的先天免疫保护与营养吸收效率之间的平衡。因此,该途径的调节对于增强肠病原体的抗性和治疗代谢性疾病可能有效。
 
据了解,肠粘膜既是摄取食物来源营养物和微生物组来源代谢物的渠道,又是防止微生物入侵组织并缓解肠道各种炎性反应的屏障。目前尚不清楚肠道如何能够在保持屏障功能的同时协调食物消耗的生理和免疫反应来优化营养吸收。
 
附:英文原文

Title: Feeding-dependent VIP neuron–ILC3 circuit regulates the intestinal barrier

Author: Jhimmy Talbot, Paul Hahn, Lina Kroehling, Henry Nguyen, Dayi Li, Dan R. Littman

Issue&Volume: 2020-02-12

Abstract: The intestinal mucosa serves as both a conduit for uptake of food-derived nutrients and microbiome-derived metabolites and as a barrier that prevents tissue invasion by microbes and tempers inflammatory responses to the myriad contents of the lumen. How the intestine coordinates physiological and immune responses to food consumption to optimize nutrient uptake while maintaining barrier functions remains unclear. Here, we describe how a gut neuronal signal triggered by food intake is integrated with intestinal antimicrobial and metabolic responses controlled by type 3 innate lymphoid cells (ILC3)1–3. Food consumption rapidly activates a population of enteric neurons that express vasoactive intestinal peptide (VIP)4. Projections of VIP-producing neurons (VIPergic neurons) in the lamina propria are in close proximity to clusters of ILC3 that selectively express VIP receptor type 2 (VIPR2 or VPAC2). ILC3 production of IL-22, which is up-regulated by commensal microbes such as segmented filamentous bacteria (SFB)5–7, is inhibited upon engagement of VIPR2. As a consequence, there is a reduction in epithelial cell-derived antimicrobial peptide, but enhanced expression of lipid-binding proteins and transporters8. During food consumption, activation of VIPergic neurons thus enhances growth of epithelial-associated SFB and increases lipid absorption. Our results reveal a feeding- and circadian-regulated dynamic intestinal neuro-immune circuit that promotes a trade-off between IL-22-mediated innate immune protection and efficiency of nutrient absorption. Modulation of this pathway may hence be effective for enhancing resistance to enteropathogen2,3,9 and for treatment of metabolic diseases.

DOI: 10.1038/s41586-020-2039-9

编辑:科学网:小柯机器人

©2020年02月17日 02:37:45
基因在线
0.072s加载完成
北京艾迪灵科技有限公司 旗下网站