创作:mildbreeze 审核:mildbreeze 03月01日
  • 肠道固有层中,表达血管活性肠肽(VIP)的肠神经元与表达VIP受体2型(VIPR2)的CCR6+ 3型天然淋巴细胞(ILC3)细胞簇存在近距离互作;
  • VIPR2活化使ILC3生成的细胞因子IL-22减少,导致肠上皮细胞(IEC)产生的RegIIIγ等抗菌肽减少,可削弱肠屏障功能(加剧肠道致病菌移位),同时IEC的脂质结合和转运蛋白表达增加;
  • 进食可快速活化VIP神经元,经VIP-ILC3轴引起肠道菌群的餐后变化,促进附于肠上皮的分节丝状菌生长,并增加脂质吸收。
Nature [IF:42.778]

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



02-12, Article

Abstract & Authors:展开

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.

First Authors:
Jhimmy Talbot

Correspondence Authors:
Dan R Littman

All Authors:
Jhimmy Talbot,Paul Hahn,Lina Kroehling,Henry Nguyen,Dayi Li,Dan R Littman