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

被引：172

作者：

Leyva-Castillo, Juan-Manuel ^{[1
]}

Galand, Claire ^{[1
,15
]}

Kam, Christy ^{[1
]}

Burton, Oliver ^{[1
,16
]}

Gurish, Michael ^{[2
]}

Musser, Melissa A. ^{[3
]}

Goldsmith, Jeffrey D. ^{[4
]}

Hait, Elizabeth ^{[5
]}

Nurko, Samuel ^{[5
]}

Brombacher, Frank ^{[6
,7
,8
]}

Dong, Chen ^{[9
,10
]}

Finkelman, Fred D. ^{[11
,12
]}

Lee, Richard T. ^{[13
]}

Ziegler, Steven ^{[14
]}

Chiu, Isaac ^{[3
]}

Austen, K. Frank ^{[2
]}

Geha, Raif S. ^{[1
]}

机构：

[1] Harvard Med Sch, Boston Childrens Hosp, Div Immunol, Boston, MA 02115 USA

[2] Harvard Med Sch, Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA

[3] Harvard Med Sch, Dept Microbiol & Immunobiol, Boston, MA 02115 USA

[4] Boston Childrens Hosp, Dept Pathol, Boston, MA USA

[5] Boston Childrens Hosp, Div Gastroenterol, Boston, MA USA

[6] Int Ctr Genet Engn & Biotechnol, Cape Town, South Africa

[7] Univ Cape Town, Rondebosch, South Africa

[8] South Africa Med Res Council, Pietermaritzburg, South Africa

[9] Tsinghua Univ, Inst Immunol, Beijing, Peoples R China

[10] Tsinghua Univ, Sch Med, Beijing, Peoples R China

[11] Cincinnati Childrens Hosp Med Ctr, Dept Internal Med, Cincinnati, OH 45229 USA

[12] Cincinnati Childrens Hosp Med Ctr, Div Immunobiol, Cincinnati, OH 45229 USA

[13] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA

[14] Benaroya Res Inst, Program Immunol, Seattle, WA USA

[15] Agenus Inc, 3 Forbes Rd, Lexington, MA 02421 USA

[16] VIB KU Leuven Ctr Brain & Dis Res, Leuven, Belgium

来源：

IMMUNITY | 2019年 / 50卷 / 05期

关键词：

INNATE LYMPHOID-CELLS; BARRIER FUNCTION; IL-33; PROMOTES; DEFICIENT MICE; TUFT CELLS; ROR-ALPHA; IGE; PERMEABILITY; SENSITIZATION; INFLAMMATION;

D O I：

10.1016/j.immuni.2019.03.023

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页码：1262 / +

页数：18

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