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

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.

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“…Lake et al provided a normalized approach and compared nuclear and whole-cell expression data ( Lake et al, 2017 ; Lake et al, 2019 ). SnRNA-seq might be more widely applied in clinical practice because it is tolerant to sample sources, such as temporal neocortical tissues ( Busch et al, 2022 ), human hippocampus ( Su et al, 2022 ), gut tissue samples ( Hung et al, 2022 ), frozen or hard-to-dissociate tumors ( Slyper et al, 2020 ). One study showed that snRNA-seq performed better on inflammatory fibrotic tissues than scRNA-seq.…”

An update on recent developments and highlights in food allergy

“…This finding highlights the importance of early introduction in potentially halting or reversing the progression of the specific FA being treated, in addition to prevention. Tissue‐specific effects of OIT in humans are under‐researched and may play an important role 99,100 …”

“…Tissue-specific effects of OIT in humans are under-researched and may play an important role. 99,100 SLIT utilizes a 100-fold lower dose of allergen (maintenance dose as reported for inhalant allergen SLIT. 101,102 Such mechanisms include the uptake of allergens by oral antigen presenting cells (APCs) from the sublingual mucosa.…”

An update on recent developments and highlights in food allergy

“…98 Tissue-specific effects of OIT in humans are under-researched and may play an important role. 99,100 SLIT utilizes a hundred-fold lower dose of allergen (maintenance dose 2-5mg/day). It takes advantage of local oral tolerance mechanisms as reported for inhalant allergen SLIT.…”