Precision cut intestinal slices, a novel model of acute food allergic reactions

Lisa Hung, Alper Celik, Xiaojun Yin, Kai Yu, Alireza Berenjy, Akash Kothari, Helena Obernolte, Julia E M Upton, Katrine Lindholm Bøgh, Gino R Somers, Iram Siddiqui, Martin Grealish, Fayez A Quereshy, Katherina Sewald, Priscilla P L Chiu, Thomas Eiwegger

Research output: Journal article (peer-reviewed)Journal article

1 Citation (Scopus)

Abstract

BACKGROUND: Food allergy affects up to 10% of the pediatric population. Despite ongoing efforts, treatment options remain limited. Novel models of food allergy are needed to study response patterns downstream of IgE-crosslinking and evaluate drugs modifying acute events. Here, we report a novel human ex vivo model that displays acute, allergen-specific, IgE-mediated smooth muscle contractions using precision cut intestinal slices (PCIS).

METHODS: PCIS were generated using gut tissue samples from children who underwent clinically indicated surgery. Viability and metabolic activity were assessed from 0-24h. Distribution of relevant cell subsets was confirmed using single nucleus RNA sequencing. PCIS were passively sensitized using plasma from peanut allergic donors or peanut-sensitized non-allergic donors, and exposed to various stimuli including serotonin, histamine, FcɛRI-crosslinker and food allergens. Smooth muscle contractions and mediator release functioned as readouts. A novel program designed to measure contractions was developed to quantify responses. The ability to demonstrate the impact of antihistamines and immunomodulation from peanut oral immunotherapy (OIT) was assessed.

RESULTS: PCIS viability was maintained for 24h. Cellular distribution confirmed the presence of key cell subsets including mast cells. The video analysis tool reliably quantified responses to different stimulatory conditions. Smooth muscle contractions were allergen-specific and reflected the clinical phenotype of the plasma donor. Tryptase measurement confirmed IgE-dependent mast cell-derived mediator release. Antihistamines suppressed histamine-induced contraction and plasma from successful peanut OIT suppressed peanut-specific PCIS contraction.

CONCLUSION: PCIS represent a novel human tissue-based model to study acute, IgE-mediated food allergy and pharmaceutical impacts on allergic responses in the gut.

Original languageEnglish
JournalAllergy: European Journal of Allergy and Clinical Immunology
Early online date14 Nov 2022
DOIs
Publication statusE-pub ahead of print - 14 Nov 2022

Keywords

  • PCIS
  • allergy model
  • food allergy
  • intestine
  • precision cut intestinal slices

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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