Precision cut intestinal slices, a novel model of acute food allergic reactions. Issue 2 (23rd November 2022)

• Record Type: Journal Article
• Authors: Hung, Lisa; Celik, Alper; Yin, Xiaojun; Yu, Kai; Berenjy, Alireza; Kothari, Akash; Obernolte, Helena; Upton, Julia E. M.; Lindholm Bøgh, Katrine; Somers, Gino R.; Siddiqui, Iram; Grealish, Martin; Quereshy, Fayez A.; Sewald, Katherina; Chiu, Priscilla P. L.; Eiwegger, Thomas
• Is Part Of: Allergy. Volume 78:Issue 2(2023)
• Page Start: 500
• Page End: 511
• Publication Date: 2022-11-23
• Subjects: allergy model -- food allergy -- intestine -- PCIS -- precision cut intestinal slices; Allergy -- Periodicals; 616.97
• DOI: 10.1111/all.15579
• Languages: English
• ISSNs: 0105-4538

Abstract

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 to 24 h. 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 24 h. 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. Abstract : A novel human ex vivo GI tissue‐based PCIS model was developed to study IgE‐mediated food allergy. PCIS were generated using healthy, non‐inflamed tissue from children. Passively sensitized PCIS displayed allergen‐specific responses including mediator release and smooth muscle contractions which correlated with the clinical reactivity of the plasma donor. Antihistamines and plasma from patients who underwent successful oral immunotherapy suppressed contraction responses.Abbreviations: GI, gastrointestinal; OIT, oral immunotherapy; PCIS, precision cut intestinal slices; SMCs, smooth muscle cells