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Review
. 2020 Dec 15;12(12):3830.
doi: 10.3390/nu12123830.

Mechanisms Underlying the Skin-Gut Cross Talk in the Development of IgE-Mediated Food Allergy

Marloes van Splunter  1 , Liu Liu  1 , R J Joost van Neerven  2   3 , Harry J Wichers  4 , Kasper A Hettinga  5 , Nicolette W de Jong  1
Affiliations
Review

Mechanisms Underlying the Skin-Gut Cross Talk in the Development of IgE-Mediated Food Allergy

Marloes van Splunter et al. Nutrients. .

Abstract

Immune-globulin E (IgE)-mediated food allergy is characterized by a variety of clinical entities within the gastrointestinal tract, skin and lungs, and systemically as anaphylaxis. The default response to food antigens, which is antigen specific immune tolerance, requires exposure to the antigen and is already initiated during pregnancy. After birth, tolerance is mostly acquired in the gut after oral ingestion of dietary proteins, whilst exposure to these same proteins via the skin, especially when it is inflamed and has a disrupted barrier, can lead to allergic sensitization. The crosstalk between the skin and the gut, which is involved in the induction of food allergy, is still incompletely understood. In this review, we will focus on mechanisms underlying allergic sensitization (to food antigens) via the skin, leading to gastrointestinal inflammation, and the development of IgE-mediated food allergy. Better understanding of these processes will eventually help to develop new preventive and therapeutic strategies in children.

Keywords: atopic dermatitis; cutaneous sensitization; food allergy; microbiota; skin-gut-axis.

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Conflict of interest statement

The authors declare no conflict of interest. RJ Joost van Neerven is in addition to his academic affiliation also employed by FrieslandCampina.

Figures

Figure 1
Figure 1
Scratching can further result in a decreased barrier function of the skin and the intestine. Scratching elicits thymic stromal lymphopoietin (TSLP) and IL-33 responses in skin activating Langerhans’ cells (LC), innate lymphoid type 2 cells (ILC2) and T helper 2 cells (Th2). Furthermore, IL-4 production of basophils (BC) enhances the type 2 responses and leads do a decrease of filaggrin (FLG) expression in combination with IL-33. Due to type 2 responses both IgE-mediated release of mast cells (MC) and migration of MCs to the intestine is increased. This results in an increased permeability of the intestine and therefore of an influx of food allergens, potentially leading to enhanced sensitization or allergic responses to these food antigens.
Figure 2
Figure 2
Food-induced anaphylaxis as a result of scratching or decreased skin barrier function. Intestinal permeability is increased due to influx of mast cells (MC) as a result of scratching or damaged skin. This results an increased entrance of food antigens in the intestine eliciting the production of TSLP, IL-33, and IL-25. IL-25 can activate ILC2 cells and IL-33 and TSLP activate dendritic cells in the lamina propia of the intestine (LP-DC), which activate Th2 cells. Th2 cells and ILC2 cells produce IL-4 and IL-13, resulting in inhibition of Tregs and stimulation of MCs. This leads to an accumulation of (sensitized) MC and IL-9 producing mucosal mast cells (MMC9) in the intestine, which causes an increased permeability of the intestine. Food allergens can passage the epithelial barrier, resulting in IgE-mediated degranulation of the MCs and as a result of mediator release, food-induced anaphylaxis.
See this image and copyright information in PMC

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MeSH terms