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

Immunity. 2019 May 21;50(5):1262-1275.e4. doi: 10.1016/j.immuni.2019.03.023. Epub 2019 Apr 23.

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.

Keywords: ILC2s; food allergy; gut; innate immunity; mast cells; skin.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • 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
  • Intestinal Mucosa / immunology*
  • Lymphocytes / immunology*
  • Male
  • Mast Cells / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Signal Transduction / immunology
  • Skin / immunology
  • Skin / injuries

Substances

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