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

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

doi:10.1038/s41586-020-2039-9

Cited by 210 publications

(192 citation statements)

References 46 publications

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“…PICRUSt1 functional prediction revealed that the rumen microbiota were regulated by the nervous system under cold temperature. Several studies have found that the gut microbiota in mice are regulated by neurons, such as VIP neurons [34]. We suspect that rumen microbes can similarly be regulated by neuronal factors.…”

Section: Discussionmentioning

confidence: 82%

Effects of Low Temperature and Wind Treatment on Physiological Indexes, Rumen Microbiota, Immune Responses and Hormones in Sheep

Guo¹,

Zhou²,

Tian³

et al. 2020

Preprint

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Background: Low-temperature environments can strongly affect the normal growth and health of livestock. Previous studies have shown that cold exposure can alter the intestinal microbiota and thereby affect other traits. In winter, cold weather can be accompanied by strong winds that aggravate the effects of cold on livestock. In this study, an experiment was conducted to investigate the effect of low temperature and wind speed on physiological indexes, rumen microbiota, and immune responses in sheep.Methods: The sheep were divided into control group and test group according to their ambient temperature.Sheep in the test group were divided into four groups according to wind-speed treatment: no wind (average wind velocity less than 0.5 m/s), low wind velocity (average wind velocity of 3 m/s), medium wind velocity (average wind velocity of 4 m/s) and high wind velocity (average wind velocity of 5 m/s).Results: Average daily gain and the utilization of forage, especially soluble fiber, decreased with increasing wind velocity in cold temperature (P<0.05). In rumen, the enzyme activity of cellulose degradation was also lowerwith increasing wind velocity (P<0.05). The abundance of potentially beneficial bacteria showed differedamong the wind treatments (P<0.05).The large fluctuations in the amount of bacteria provided a breeding opportunity forpotentially harmful bacteria (P<0.05). In addition, there were significant decreases in the serum levels of IL-2 and IFN-γ (P<0.05) and a large increase in IL-4 level (P<0.05), which indicated that the sheep underwent immune suppressionduring the trial. The significant increase in the activities of the antioxidant enzymes SOD, GSH-PX, and CAT (P<0.05) indicated that the production of oxygen free radicals was increased.Conclusions: The cold environment significantly reduced the growth of sheep and altered the composition of rumen microbiota, reducing the utilization of soluble fiber by the rumen flora. Furthermore, the sheep produced large amounts of enzymes to resist tissue damage and experienced immune suppression in the cold environment.

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Section: Discussionmentioning

confidence: 82%

Effects of Low Temperature and Wind Treatment on Physiological Indexes, Rumen Microbiota, Immune Responses and Hormones in Sheep

Guo¹,

Zhou²,

Tian³

et al. 2020

Preprint

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“…Additional neurotransmitters include, gamma-Aminobutyric acid (GABA), epinephrine and dopamine, but also vasoactive intestinal peptide (VIP), neuromedin U (NMU), calcitonin gene-related peptide (CGRP), Substance P, Galanin, Tachykinin, and others (32,35). With regard to neuronal regulation of immune responses, the biochemical signature of the neuron (neurotransmitters, neuropeptides) appear to be functionally most relevant, since many of the neuropeptides such as VIP, NMU, CGRP regulate immune responses via different subsets of immune cells (36)(37)(38)(39)(40)(41)(42)(43)(44). The in-depth characterization of enteric neurons may allow to identify neuronal subsets based on the expression of neurotransmitters/neuropeptides and to assign specific inflammatory functions analog to immune cells.…”

Section: Extrinsic Innervationmentioning

confidence: 99%

“…Within intestinal tissues, ILCs and nerves show a close co-localization, which presumably supports neuronal regulation of ILC responses. Enteric neurons express the neuropeptides NMU, VIP, and CGRP whereas the receptors for these neuropeptides are expressed on ILCs (Figure 3B) (37)(38)(39)(40)(41)(42)(43)(44).…”

Section: Innate Lymphoid Cells (Ilcs)mentioning

confidence: 99%

“…A study by Talbot and colleagues found that CCR6 + ILC3s but not CCR6 − ILC3s, in cryptopatches expressed Vipr2 and additional molecules related to neuro-immune interaction. CCR6 + ILC3s are an important source of IL-22, which regulates epithelial function including production of antimicrobial peptides and lipid absorption and thereby adapting the immune control to nutrient uptake (44). While the VIP-VIPR2 pathway links antimicrobial immunity, circadian rhythm and food adsorption, whether ILC3 are stimulated or inhibited by VIP is controversial.…”

Section: Innate Lymphoid Cells (Ilcs)mentioning

confidence: 99%

“…(23,(36)(37)(38)(39)(40)(41)(42)44, The complex interactions of the enteric nervous system with innate and adaptive immune cells. (A) Representation of the close co-localization of extrinsic neuronal fibers and immune cells in the intestine.…”

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confidence: 99%

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Neuro-Immune Circuits Regulate Immune Responses in Tissues and Organ Homeostasis

2020

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The dense innervation of the gastro-intestinal tract with neuronal networks, which are in close proximity to immune cells, implies a pivotal role of neurons in modulating immune functions. Neurons have the ability to directly sense danger signals, adapt immune effector functions and integrate these signals to maintain tissue integrity and host defense strategies. The expression pattern of a large set of immune cells in the intestine characterized by receptors for neurotransmitters and neuropeptides suggest a tight neuronal hierarchical control of immune functions in order to systemically control immune reactions. Compelling evidence implies that targeting neuro-immune interactions is a promising strategy to dampen immune responses in autoimmune diseases such as inflammatory bowel diseases or rheumatoid arthritis. In fact, electric stimulation of vagal fibers has been shown to be an extremely effective treatment strategy against overwhelming immune reactions, even after exhausted conventional treatment strategies. Such findings argue that the nervous system is underestimated coordinator of immune reactions and underline the importance of neuro-immune crosstalk for body homeostasis. Herein, we review neuro-immune interactions with a special focus on disease pathogenesis throughout the gastro-intestinal tract.

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