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Pathophysiological Roles of Neuro-Immune Interactions between Enteric Neurons and Mucosal Mast Cells in the Gut of Food Allergy Mice
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Pathophysiological Roles of Neuro-Immune Interactions between Enteric Neurons and Mucosal Mast Cells in the Gut of Food Allergy Mice
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Journal Article
Pathophysiological Roles of Neuro-Immune Interactions between Enteric Neurons and Mucosal Mast Cells in the Gut of Food Allergy Mice
2021
Overview
Recently, the involvement of the nervous system in the pathology of allergic diseases has attracted increasing interest. However, the precise pathophysiological role of enteric neurons in food allergies has not been elucidated. We report the presence of functional high-affinity IgE receptors (FcεRIs) in enteric neurons. FcεRI immunoreactivities were observed in approximately 70% of cholinergic myenteric neurons from choline acetyltransferase-eGFP mice. Furthermore, stimulation by IgE-antigen elevated intracellular Ca2+ concentration in isolated myenteric neurons from normal mice, suggesting that FcεRIs are capable of activating myenteric neurons. Additionally, the morphological investigation revealed that the majority of mucosal mast cells were in close proximity to enteric nerve fibers in the colonic mucosa of food allergy mice. Next, using a newly developed coculture system of isolated myenteric neurons and mucosal-type bone-marrow-derived mast cells (mBMMCs) with a calcium imaging system, we demonstrated that the stimulation of isolated myenteric neurons by veratridine caused the activation of mBMMCs, which was suppressed by the adenosine A3 receptor antagonist MRE 3008F20. Moreover, the expression of the adenosine A3 receptor gene was detected in mBMMCs. Therefore, in conclusion, it is suggested that, through interaction with mucosal mast cells, IgE-antigen-activated myenteric neurons play a pathological role in further exacerbating the pathology of food allergy.
Publisher
MDPI AG,MDPI
Subject
/ Adenosine A3 Receptor Antagonists - pharmacology
/ Animals
/ Antigens
/ Bone Marrow Cells - drug effects
/ Bone Marrow Cells - pathology
/ Cell Communication - drug effects
/ Choline
/ Colon
/ Diarrhea
/ Enteric Nervous System - drug effects
/ Enteric Nervous System - immunology
/ Enteric Nervous System - physiopathology
/ FcεRI
/ Food Hypersensitivity - immunology
/ Food Hypersensitivity - physiopathology
/ Intestinal Mucosa - drug effects
/ Intestinal Mucosa - immunology
/ Intestinal Mucosa - physiopathology
/ Intracellular Space - metabolism
/ Ligands
/ Male
/ Mice
/ Mucosa
/ Myenteric Plexus - metabolism
/ Neurons
/ Receptor, Adenosine A3 - genetics
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