Vagus nerve stimulation dampens intestinal inflammation in a murine model of experimental food allergy.
Allergens
Animals
Biomarkers
Cell Membrane Permeability
Disease Models, Animal
Food Hypersensitivity
/ diagnosis
Gastroenteritis
/ etiology
Immunophenotyping
Macrophages
/ immunology
Mast Cells
/ immunology
Mastocytosis
Mice
Mice, Knockout
Neutrophil Infiltration
/ immunology
Ovalbumin
/ immunology
Severity of Illness Index
Vagotomy
Vagus Nerve Stimulation
alpha7 Nicotinic Acetylcholine Receptor
/ genetics
CX3CR1 macrophages
cholinergic anti-inflammatory pathway
food allergy
mast cells
vagus nerve stimulation
Journal
Allergy
ISSN: 1398-9995
Titre abrégé: Allergy
Pays: Denmark
ID NLM: 7804028
Informations de publication
Date de publication:
09 2019
09 2019
Historique:
received:
17
12
2018
revised:
29
01
2019
accepted:
18
02
2019
pubmed:
22
3
2019
medline:
5
8
2020
entrez:
22
3
2019
Statut:
ppublish
Résumé
The vagus nerve has emerged as an important modulator of the intestinal immune system. Its anti-inflammatory properties have been previously shown in innate and Th1/Th17 predominant inflammatory models. To what extent the vagus nerve is of importance in Th2 inflammatory responses like food allergy is still unclear. In this study, we therefore aimed to investigate the effect of vagotomy (VGX) and vagus nerve stimulation (VNS), on the development and severity of experimental food allergy. Balb/C mice were first sensitized with ovalbumin (OVA) in the presence of alum. Prior to oral challenges with OVA, mice were subjected to VGX or VNS. Disease severity was determined by assessing severity and onset of diarrhoea, OVA-specific antibody production, mast cell number and activity, inflammatory gene expression in duodenal tissue and lamina propria immune cells by flow cytometry analysis. When compared to control mice, VGX did not significantly affect the development and severity of the disease in our model of food allergy. VNS, on the other hand, resulted in a significant amelioration of the different inflammatory parameters assessed. This effect was independent of α7nAChR and is possibly mediated through the dampening of mast cells and increased phagocytosis of OVA by CX3CR1 These results underscore the anti-inflammatory properties of the vagus nerve and the potential of neuro-immune interactions in the intestine. Further insight into the underlying mechanisms could ultimately lead to novel therapeutic approaches in the treatment of not only food allergy but also other immune-mediated diseases.
Sections du résumé
BACKGROUND
The vagus nerve has emerged as an important modulator of the intestinal immune system. Its anti-inflammatory properties have been previously shown in innate and Th1/Th17 predominant inflammatory models. To what extent the vagus nerve is of importance in Th2 inflammatory responses like food allergy is still unclear. In this study, we therefore aimed to investigate the effect of vagotomy (VGX) and vagus nerve stimulation (VNS), on the development and severity of experimental food allergy.
METHODS
Balb/C mice were first sensitized with ovalbumin (OVA) in the presence of alum. Prior to oral challenges with OVA, mice were subjected to VGX or VNS. Disease severity was determined by assessing severity and onset of diarrhoea, OVA-specific antibody production, mast cell number and activity, inflammatory gene expression in duodenal tissue and lamina propria immune cells by flow cytometry analysis.
RESULTS
When compared to control mice, VGX did not significantly affect the development and severity of the disease in our model of food allergy. VNS, on the other hand, resulted in a significant amelioration of the different inflammatory parameters assessed. This effect was independent of α7nAChR and is possibly mediated through the dampening of mast cells and increased phagocytosis of OVA by CX3CR1
CONCLUSIONS
These results underscore the anti-inflammatory properties of the vagus nerve and the potential of neuro-immune interactions in the intestine. Further insight into the underlying mechanisms could ultimately lead to novel therapeutic approaches in the treatment of not only food allergy but also other immune-mediated diseases.
Identifiants
pubmed: 30897213
doi: 10.1111/all.13790
pmc: PMC6790670
doi:
Substances chimiques
Allergens
0
Biomarkers
0
alpha7 Nicotinic Acetylcholine Receptor
0
Ovalbumin
9006-59-1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1748-1759Subventions
Organisme : European Research Council (ERC)
ID : ERC-2013-Adg: 340101 Cholstim
Pays : International
Organisme : FWO
ID : G.0566.12N
Pays : International
Organisme : FWO
ID : G.0D83.17N
Pays : International
Organisme : Postdoctoral research fellowship of FWO
Pays : International
Organisme : FWO PhD fellowship
ID : 1110019N
Pays : International
Organisme : FWO PhD fellowship
ID : 11Y2116N
Pays : International
Organisme : KU Leuven
ID : ZKD2906-C14/17/097
Pays : International
Organisme : KU Leuven
ID : ZKC9531-C12/15/016
Pays : International
Informations de copyright
© 2019 The Authors. Allergy Published by John Wiley & Sons Ltd.
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