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Immunity. 2019 Apr 10. pii: S1074-7613(19)30140-2. doi: 10.1016/j.immuni.2019.03.023. [Epub ahead of print]

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

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Division of Immunology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA.
Department of Pathology, Boston Children's Hospital, Boston, MA, USA.
Division of Gastroenterology, Boston Children's Hospital, Boston, MA, USA.
International Center for Genetic Engineering and Biotechnology & University of Cape Town & South Africa Medical Research Council, South Africa.
Institute for Immunology and School of Medicine, Tsinghua University, Beijing, China.
Department of Internal Medicine and Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA.
Immunology Program, Benaroya Research Institute, Seattle, WA, USA.
Division of Immunology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address:


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.


ILC2s; food allergy; gut; innate immunity; mast cells; skin

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