Mechanisms of gastrointestinal allergic disorders
Nurit P. Azouz, Marc E. Rothenberg
Nurit P. Azouz, Marc E. Rothenberg
Published March 11, 2019
Citation Information: J Clin Invest. 2019;129(4):1419-1430. https://doi.org/10.1172/JCI124604.
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Review Series

Mechanisms of gastrointestinal allergic disorders

Abstract

Gastrointestinal (GI) allergic disease is an umbrella term used to describe a variety of adverse, food antigen–driven, immune-mediated diseases. Although these diseases vary mechanistically, common elements include a breakdown of immunologic tolerance, a biased type 2 immune response, and an impaired mucosal barrier. These pathways are influenced by diverse factors such as diet, infections, exposure to antibiotics and chemicals, GI microbiome composition, and genetic and epigenetic elements. Early childhood has emerged as a critical period when these factors have a dramatic impact on shaping the immune system and therefore triggering or protecting against the onset of GI allergic diseases. In this Review, we will discuss the latest findings on the molecular and cellular mechanisms that govern GI allergic diseases and how these findings have set the stage for emerging preventative and treatment strategies.

Authors

Nurit P. Azouz, Marc E. Rothenberg

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Figure 2

The effects of different allergen exposure paths on GI allergic diseases.

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The effects of different allergen exposure paths on GI allergic diseases...
(A) The dual allergen exposure hypothesis suggests that (a) environmental exposure to antigens in early life, specifically via the skin, increases the risk of developing food allergic disease later in life by inducing allergic sensitization, and (b) oral consumption of high amounts of antigen in early life decreases the risk of developing food allergic disease later in life by inducing immune tolerance. (B) OIT induces Treg expansion and release of IL-10. IL-10 promotes Treg cell differentiation and inhibits Th2 cell differentiation. As a result, less IL-4 is produced, which decreases IgE isotype switch recombination in local B cells and Th2 cell differentiation. OIT-induced TGF-β production by Tregs is also considered pathogenic in EoE and promotes tissue fibrosis, epithelial-to-mesenchymal transition, and smooth muscle contraction. OIT, at least in the setting of EoE, does not effectively dampen Th2 cell production of IL-5 and IL-13, which promote EoE. Increased IgG4 production by B cells is thought to be protective against IgE-mediated allergic GI diseases but might be pathogenic in EoE.