餵食依賴性VIP神經元與ILC3之間的迴路調節腸道屏障
作者：
小柯機器人發布時間：2020/2/14 15:16:21
美國紐約大學醫學院Dan R. Littman研究小組發現，餵食依賴性VIP神經元與ILC3之間的迴路調節腸道屏障。該項研究成果2020年2月12日在線發表在《自然》上。
研究人員報導了食物攝入觸發的腸道神經元信號如何與由3型先天性淋巴樣細胞（ILC3）控制的腸道抗菌和代謝反應進行整合。食物攝取會迅速激活表達血管活性腸肽（VIP）的腸道神經元。固有層中產生VIP的神經元（VIPergic神經元）的投影非常接近選擇性表達2型VIP受體（VIPR2或VPAC2）的ILC3。ILCR3產生的IL-22（被共生的微生物所上調，如節段性絲狀細菌SFB）被VIPR2所抑制。因此，上皮細胞產生的抗菌肽減少，但脂質結合蛋白和轉運蛋白的表達增加。在食物攝取期間，VIPergic神經元的激活增強了上皮相關SFB的生長並增加了脂質吸收。這些研究結果揭示了一種餵食和晝夜調節的動態腸道神經免疫迴路，其可促進IL-22介導的先天免疫保護與營養吸收效率之間的平衡。因此，該途徑的調節對於增強腸病原體的抗性和治療代謝性疾病可能有效。
據了解，腸黏膜既是攝取食物來源營養物和微生物組來源代謝物的渠道，又是防止微生物入侵組織並緩解腸道各種炎性反應的屏障。目前尚不清楚腸道如何能夠在保持屏障功能的同時協調食物消耗的生理和免疫反應來優化營養吸收。
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
Source: https://www.nature.com/articles/s41586-020-2039-9