Mechanical Skin Injury Promotes Food Anaphylaxis by Driving Intestinal Mast Cell Expansion.

Abstract

Mast cell (MC) mediator release after crosslinking of surface-bound IgE antibody by ingested antigen underlies food allergy. However, IgE antibodies are not uniformly associated with food allergy, and intestinal MC load is an important determinant. Atopic dermatitis (AD), characterized by pruritis and cutaneous sensitization to allergens, including foods, is strongly associated with food allergy. Tape stripping mouse skin, a surrogate for scratching, caused expansion and activation of small intestinal MCs, increased intestinal permeability, and promoted food anaphylaxis in sensitized mice. Tape stripping caused keratinocytes to systemically release interleukin-33 (IL-33), which synergized with intestinal tuft-cell-derived IL-25 to drive the expansion and activation of intestinal type-2 innate lymphoid cells (ILC2s). These provided IL-4, which targeted MCs to expand in the intestine. Duodenal MCs were expanded in AD. In addition to promoting cutaneous sensitization to foods, scratching may promote food anaphylaxis in AD by expanding and activating intestinal MCs.

• Authors: Juan-Manuel Leyva-Castillo, Claire Galand, Christy Kam, Oliver Burton, Michael Gurish, Melissa A Musser, Jeffrey D Goldsmith, Elizabeth Hait, Samuel Nurko, Frank Brombacher, Chen Dong, Fred D Finkelman, Richard T Lee, Steven Ziegler, Isaac Chiu, K Frank Austen, Raif S Geha
• Journal: Immunity (Immunity) Vol. 50 Issue 5 Pg. 1262-1275.e4 (05 21 2019) ISSN: 1097-4180 [Electronic] United States
• PMID: 31027995 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2019 Elsevier Inc. All rights reserved.

Chemical References

• Il33 protein, mouse
• Il4 protein, mouse
• Interleukin-13
• Interleukin-33
• Interleukins
• Mydgf protein, mouse
• Interleukin-4
• Immunoglobulin E

Topics

• Adolescent
• Anaphylaxis (immunology)
• Animals
• Cell Proliferation
• Child
• Child, Preschool
• Dermatitis, Atopic (immunology)
• Female
• Food Hypersensitivity (immunology)
• Humans
• Immunoglobulin E (immunology)
• Interleukin-13 (metabolism)
• Interleukin-33 (metabolism)
• Interleukin-4 (metabolism)
• Interleukins (metabolism)
• Intestinal Mucosa (cytology, immunology)
• Lymphocytes (immunology)
• Male
• Mast Cells (immunology)
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Signal Transduction (immunology)
• Skin (immunology, injuries)