Leyva-Castillo JM, Galand C, Kam C, Burton O, Gurish M, Musser MA, Goldsmith JD, Hait E, Nurko S, Brombacher F, Dong C, Finkelman FD, Lee RT, Ziegler S, Chiu I, Austen KF, Geha RS. Mechanical Skin Injury Promotes Food Anaphylaxis by Driving Intestinal Mast Cell Expansion. Immunity. 2019 05 21; 50(5):1262-1275.e4.

Citation

Leyva-Castillo JM, Galand C, Kam C, Burton O, Gurish M, Musser MA, Goldsmith JD, Hait E, Nurko S, Brombacher F, Dong C, Finkelman FD, Lee RT, Ziegler S, Chiu I, Austen KF, Geha RS. 2019. Mechanical Skin Injury Promotes Food Anaphylaxis by Driving Intestinal Mast Cell Expansion. Immunity. 50(5):1262-1275.e4. Pubmed: 31027995 DOI:S1074-7613(19)30140-2

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.

Related Faculty

Richard Lee, M.D.

Lee Lab

Rich Lee seeks to understand heart failure and metabolic diseases that accompany human aging, and translate that understanding into therapies. Lee is an active clinician, regularly treating patients at Brigham and Women’s Hospital.