Mechanisms Underlying the Skin-Gut Cross Talk in the Development of IgE-Mediated Food Allergy
Abstract
:1. Introduction
2. Skin Barrier and Skin Sensitization
- Skin is an important permeability and immune barrier.
- Disrupted skin barrier leads to increased sensitization to food allergens in the skin.
3. Environmental Factors Induce Sensitization to Food Allergens via the Skin
- Detergents and environmental allergens, like house dust mite or Alternaria alternata allergens, can disrupt skin barrier.
- Cutaneous exposure of allergens prior to ingestion leads to increased sensitization.
- Tolerance is induced if allergens are ingested prior to cutaneous exposure.
4. TSLP-Mediated Type 2 Inflammation in the Skin
- Disrupted skin barrier leads to increased sensitization to food allergens in the skin. This process is mediated by TSLP-induced DC and basophils, producing IL-4 and resulting in enhanced type 2 responses.
5. Major Role for Type 2 Innate Lymphoid Cells (ILC2) and Epithelial Cytokines in the Development of Food Allergy
- Skin damage results in the release of IL-33, TSLP.
- Specifically, IL-33 cells activate DCs and ILC2 cells.
- Through activating ILC2 cells and DCs, epithelial cytokines, e.g., TSLP and IL-25, can mediate a type 2 inflammation reaction in an antigen independent manner.
6. How Can Pruritus Lead to Food-Induced Anaphylaxis?
- Scratching induces enhanced IL-33 levels in the skin and in serum.
- IL-33 together with IL-4 and Th2 cells are able to induce accumulation of mast cells and IL-9 producing mucosal mast cells (MMC9) in the intestine.
- IL-33 results in more IgE-mediated degranulation of these MCs and MMC9 cells, leading to food allergy.
- Scratching increases numbers of intestinal mast cells and increased permeability of the intestines resulting in the development of food allergy.
- A skin-to-gut axis is inevitable as food allergy symptoms in the intestine apparently can be induced by increased IL-33 levels in serum, which is induced by a damaged skin barrier due to scratching or AD.
7. The Role of Skin Microbiota in the Development of Food Allergy
- Staphylococcus aureus colonization is related to reduce microbial diversity in the skin and increased prevalence of atopic dermatitis and food allergy.
8. The Role of Intestinal Microbiota on the Development of Atopy and Atopic Dermatitis
- There is no conclusive evidence that specific microbial species are responsible for the development of allergy or atopic dermatitis.
- Short chain fatty acids produced by intestinal microbiota are linked to reduced allergic inflammation.
9. Future Human Research Priorities
10. Conclusions
Author Contributions
Funding
Conflicts of Interest
Glossary of Terms
ATP | Adenosine triphosphate |
AD | atopic dermatitis |
DC | dendritic cell |
FLG | Filaggrin |
HDM | House dust mite |
Ig | Immune globuline |
IL | interleukin |
ILC | innate lymphoid cells |
LPS | lipopolysaccharide |
MC | mast cells |
MMC9 | IL-9-producing mucosal mast cell |
OVA | ovalbumin |
SCFA | short chain fatty acids |
SDS | sodium dodecyl sulfate |
S. aureus | Staphylococcus aureus |
TEWL | transepidermal water loss |
Th2 | T helper cell 2 |
TSLP | thymic stromal lymphopoietin |
Treg | regulatory T cell |
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van Splunter, M.; Liu, L.; van Neerven, R.J.J.; Wichers, H.J.; Hettinga, K.A.; de Jong, N.W. Mechanisms Underlying the Skin-Gut Cross Talk in the Development of IgE-Mediated Food Allergy. Nutrients 2020, 12, 3830. https://doi.org/10.3390/nu12123830
van Splunter M, Liu L, van Neerven RJJ, Wichers HJ, Hettinga KA, de Jong NW. Mechanisms Underlying the Skin-Gut Cross Talk in the Development of IgE-Mediated Food Allergy. Nutrients. 2020; 12(12):3830. https://doi.org/10.3390/nu12123830
Chicago/Turabian Stylevan Splunter, Marloes, Liu Liu, R.J. Joost van Neerven, Harry J. Wichers, Kasper A. Hettinga, and Nicolette W. de Jong. 2020. "Mechanisms Underlying the Skin-Gut Cross Talk in the Development of IgE-Mediated Food Allergy" Nutrients 12, no. 12: 3830. https://doi.org/10.3390/nu12123830