Nature: After eating, the intestinal barrier strike is what causes the unexpected ending.

Click the blue word to notice that our intestinal barrier is a multi-layer system, which is composed of microbial layer, mucus layer, epithelial cell layer and immune cell layer from the intestinal cavity.intestinal mucosa can not only absorb nutrients from food sources and metabolites from microorganisms, but also prevent microbial invasion into tissues.Natural lymphocytes (ILCs) are a new type of innate immune cells which are different from T cells and B cells and have the characteristics of adaptive immune cells. Among them, type 3 natural lymphocytes (ilc3) are mainly distributed in intestinal mucosa and play an important role in maintaining intestinal barrier function. The innate immune response mediated by ILCs is to resist various pathogens The first line of defense for microbes.under physiological homeostasis, ilc3 can maintain the integrity of intestinal epithelium and mucus, promote intestinal immunity and maintain metabolic homeostasis. This process is complex. It integrates the clues of cytokine mediated and glial cell origin, and transmits the information from the lumen flora to the intestinal epithelial cells (IEC) and the cells in the lamina propria.if ilc3 regulation is abnormal, it can promote adaptive immune response, induce flora imbalance and lead to intestinal pathological damage.ilc3 activation is regulated by cytokines such as IL-23 and IL-1 β, which are produced by mononuclear phagocytes and induced by intestinal microbial derived stimulants.what kind of reaction does ilc3 make during food intake.on February 12, 2020, nature published an online article in the form of "accelerated article preview" by Professor Dan R. Littman of New York University School of medicine, revealing how intestinal barrier works in the process of diet.transcriptome analysis of different types of natural lymphocytes in the gut revealed that ilc3 had a subset of cells (CCR6 positive ilc3, which selectively expressed chemokine receptor CCR6, known as CCR6 positive ilc3), selectively expressed a variety of neurotransmitters and neuropeptide receptors, as well as genes related to axonal guidance and neuronal differentiation.it was further found that CCR6 positive ilc3 expressed vasoactive intestinal peptide receptor 2 (VIPR2).immunofluorescence assay further found that ilc3 was close to the neurons in the lamina propria. These neurons expressed vasoactive intestinal peptide (VIP), but did not express substance P (a neuropeptide in nerve fibers) or tyrosine hydroxylase. These results suggest that VIP neurons may play a key role in the regulation of intestinal immune homeostasis by CCR6 positive ilc3.compared with normal mice, the ileum CCR6 positive ilc3 produced more IL-22 and IL-17A than normal mice. However, the total amount of IL-17A produced by CCR6 positive ilc3 was not very high.therefore, the researchers believe that ilc3 may regulate barrier function through vip-vipr2 signaling pathway.inhibition of VIP positive neurons by chemical genetics resulted in more CCR6 positive ilc3 in large intestine and small intestine, and increased IL-22 and regiii γ expression. However, the production of IL-22 and the expression of regiii γ were decreased after VIP positive neurons were activated.these results suggest that VIP positive neurons are required for CCR6 positive ilc3 to play an immunoprotective role.what is regiii γ? It is a new antimicrobial peptide, mainly expressed in the intestine and skin of mammals. It has the physiological functions of antibacterial, anti-inflammatory, regulating immune response and promoting cell proliferation. Studies have shown that IL-22 can promote the production of regiii γ.in addition to exogenous activation of VIP neurons, there is also a non-destructive, purely natural way of activation, that is to eat and keep eating. food consumption can rapidly activate intestinal neurons expressing vasoactive intestinal peptide (VIP). compared with fasting for 6 hours, there were more VIP in portal vein after 6 hours of food consumption, but IL-22 produced by CCR6 positive ilc3 was decreased. What's more, chemical genetic inhibition of VIP positive neurons can offset the decrease of IL-22 caused by food consumption. this suggests that food intake inhibits CCR6 positive ilc3 production of cytokine IL-22 through VIP enteric neurons. food intake significantly affected the morphology of intestinal epithelial associated segmented filamentous bacteria (SFB). After 12 hours of feeding, the long filaments of SFB attached to intestinal epithelial cells were segmented and promoted lipid absorption. however, there were few segments of epithelial associated SFB in the 12 hour fasting mice. in addition, the study further found that the disorder of eating schedule may reduce the intestinal barrier function and promote malnutrition (the attention of irregular eating partners). in fact, on December 25, 2019, Nature Immunology published the neuropeptide VIP conferrs antimicrobial immunity by regulating ilc3 We found that the immune response of intestinal ilc3 depends on the food induced neuropeptide VIP. Intestinal ilc3 has high expression of vasoactive intestinal peptide receptor 2 (VIPR2), and VIP activation significantly enhances the production of IL-22 and epithelial barrier function. these results partially coincide with those in this paper. I don't know if this is one of the reasons to speed up the review. at the same time, we also noticed that eating can reduce antibacterial activity. Is this good or bad for humans? In conclusion, this study reveals an important gut neuro immune circuit: VIP neurons activated by feeding inhibit the intestinal flora dependent CCR6 positive ilc3 function, thereby reducing the production of IL-22 and increasing the efficiency of lipid absorption. simply put, eating activates intestinal neurons, inhibits cytokine production, and reduces antimicrobial activity, which is a bit surprising. References: 1.the role of type 3 natural lymphocytes in intestinal barrier 2. Talbot, J. Et al. Feeding dependent VIP neuron – ilc3 circuit regulations the internal barrier. Nature (comprehensive report): in the same field, nature withdraws the manuscript first, and then Science publishes the article ● special report: deeply understanding the anti new pneumonia "star of hope" redcivir ● what it means to dynamically observe AMPA receptor in human body! Vascular endothelial growth factor promotes brain lymphatic vessels to play an anti nervous system tumor role? Special thanks: