Pathophysiological roles of neuro-immune interactions between enteric neurons and mucosal mast cells in the gut of food allergy mice

Tomoe Yashiro, Hanako Ogata, Syed Faisal Zaidi, Jaemin Lee, Shusaku Hayashi, Takashi Yamamoto, Makoto Kadowaki*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

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 co-culture 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 myen-teric neurons by veratridine caused the activation of mBMMCs, which was suppressed by the aden-osine 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.

Original languageEnglish
Article number1586
JournalCells
Volume10
Issue number7
DOIs
StatePublished - 2021/07

Keywords

  • Adenosine
  • Enteric neuron
  • FcεRI
  • Food allergy
  • Mucosal mast cell
  • Neuro-immune interaction

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology

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