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Precision cut intestinal slices, a novel model of acute food allergic reactions
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  • Lisa Hung,
  • Alper Celik,
  • Xiaojun Yin,
  • Kai Yu,
  • Alireza Berenjy,
  • Akash Kothari,
  • Helena Obernolte,
  • Julia Upton,
  • Katrine Lindholm Bøgh,
  • Gino R. Somers,
  • Iram Siddiqui,
  • Martin Grealish,
  • Fayez A. Quereshy,
  • Katherina Sewald ,
  • Priscilla P.L. Chiu,
  • Thomas Eiwegger
Lisa Hung
SickKids Research Institute
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Alper Celik
SickKids Research Institute
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Xiaojun Yin
SickKids Research Institute
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Kai Yu
University Health Network
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Alireza Berenjy
SickKids Research Institute
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Akash Kothari
SickKids Research Institute
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Helena Obernolte
Fraunhofer-Institut fur Toxikologie und Experimentelle Medizin ITEM
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Julia Upton
University of Toronto Temerty Faculty of Medicine
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Katrine Lindholm Bøgh
Danmarks Tekniske Universitet
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Gino R. Somers
The Hospital for Sick Children
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Iram Siddiqui
The Hospital for Sick Children
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Martin Grealish
University Health Network
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Fayez A. Quereshy
University Health Network
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Katherina Sewald
Fraunhofer-Institut fur Toxikologie und Experimentelle Medizin ITEM
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Priscilla P.L. Chiu
The Hospital for Sick Children
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Thomas Eiwegger
SickKids Research Institute
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Abstract

Background: Food allergy affects up to 8% 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 cell nuclear 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.
21 Sep 2022Submitted to Allergy
22 Sep 2022Assigned to Editor
22 Sep 2022Submission Checks Completed
22 Sep 2022Reviewer(s) Assigned