INTRODUCTION
Food allergy (FA) is a growing public health concern.1Current estimates report 7.6% of children and 10.8% of adults are
affected by FA in the United States alone.2,3 While
many children outgrow their allergy over time, some FAs persist into
adulthood resulting in a chronic disorder. The symptoms of an allergic
reaction can be unpredictable and may result in potentially fatal
anaphylaxis.4 The current treatment approaches for FA
are limited to avoidance of the allergen and emergency interventions
upon accidental exposure, although allergen-specific immunotherapies
(e.g., oral, sublingual, epicutaneous) are a promising potential
treatment option for certain individuals.
The gastrointestinal (GI) tract plays a central role in FA as the site
of exposure and immune response to food allergens. The gut is enriched
with mast cells that are one of the primary effector cells of the
allergic response.5 They express the high affinity IgE
receptor (FcɛRI) that binds allergen-specific IgE antibodies. Upon
exposure to a relevant allergen, the receptor-bound IgE recognizes the
allergen and crosslinks the receptors, activating the
cell.6 This results in the release of pre-formed
(e.g., histamine, tryptase, serotonin) and de novo synthesized
(e.g., cytokines, leukotrienes) inflammatory mediators influencing both
local and systemic allergic responses.7 The release of
histamine causes increased intestinal smooth muscle contraction by
binding to histamine receptors in the GI tract, which may manifest as
abdominal pain during an allergic reaction.8–11Similarly, other symptoms of an acute allergic reaction are often GI
based (e.g., cramping, emesis, diarrhea) and reflect the direct andin situ immune response.12
Due to the inaccessibility of the gut, allergic exposure and the
resulting immune cascade within human GI tissues remain understudied.
Models of FA that reflect the complexity of human intestinal tissue,
including the immune system and the functionality of the enteric nervous
system, are rare.13
Precision cut intestinal slices (PCIS) are viable gut explants of a
fixed thickness that maintain the structure and cellular diversity of
intestinal
tissue.14 They
contain all relevant cell populations of interest and preserve the
spatial distribution of the distinct cell subsets.15PCIS can potentially represent any region of the intestine based on the
surgical tissue harvested. To date, the PCIS system has been used to
study the metabolism, toxicity, and interaction of pharmaceuticals as
well as models for viral infection and intestinal
fibrosis.16–21However, the use of PCIS has not yet been reported in the context of FA.
Here we report that human PCIS can be used as a model of FA to study
acute, IgE-mediated allergic reactions via measurement of smooth muscle
contraction as a readout for allergic response.