Intestinal mast cell-derived leukotrienes mediate the anaphylactic response to ingested antigens

• 成果类型: Article
• 署名作者: Bachtel, Nathaniel D.; Cullen, Jaime L.; Liu, Min; Erickson, Steven A.; Kutyavin, Vassily I.; El-Naccache, Darine W.; Florsheim, Esther B.; Lim, Jaechul; Sullivan, Zuri A.; Imaeda, Raiden; Hudak, Andrew; Zhang, Cuiling; Medzhitov, Ruslan
• 署名单位: Yale University; Arizona State University; Arizona State University-Tempe; Seoul National University (SNU); Seoul National University (SNU); Harvard University; Howard Hughes Medical Institute; Yale University; AstraZeneca
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-11340
• DOI: 10.1126/science.adp0246
• 发表日期: 2025-08-07
• 关键词: gene disruption reveals; innate lymphoid-cells; vascular-permeability; integrin alpha(v)beta(6); cardiopulmonary changes; systemic-anaphylaxis; in-vivo; ige; expression; receptor

摘要

Anaphylaxis is a life-threatening complication of food allergen exposure. Although mechanisms governing anaphylaxis after intravenous injection are defined in mice, these models neglect mucosal exposure that accompanies ingestion. We investigated the role of mast cells within the intestine of mice and found that oral anaphylaxis required immunoglobulin E-Fc epsilon receptor 1 (IgE-Fc epsilon R1) signaling. Intestinal mast cells were a heterogeneous population, shaped by epithelial cues. Compared with connective tissue mast cells found throughout the body, intestinal mast cells largely resided in the epithelium, displayed divergent transcriptomes and effector functions, and had a diminished ability to generate histamine, but they enhanced leukotriene synthesis. Mice genetically deficient in cysteinyl leukotriene synthesis, or those treated with the arachidonate 5-lipoxygenase (aLOX5) antagonist zileuton, were protected from oral antigen-induced responses, whereas those elicited by intravenous injection were unaltered.