Hoyt Laura R, Liu Elise, Olson Eli C, Jacobsen Danielle R, Siniscalco Emily R, Krier-Burris Rebecca A, Greenfield Kara G, McBride Caleb D, Alfajaro Mia M, Amat Julien A R, Zhao Zhe, Xu Lan, Philip Vivek, Verma Aditi, Fourati Slim, Senger Donna L, Zhang Lingdi, Bunyavanich Supinda, Glass Sarah E, Coffey Robert J, Wilen Craig B, Williams Adam, Eisenbarth Stephanie C
Department of Laboratory Medicine, Yale University School of Medicine, New Haven, CT, USA.
Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA.
Science. 2025 Aug 7;389(6760):eadp0240. doi: 10.1126/science.adp0240.
Food-specific immunoglobulin E (IgE) triggers life-threatening anaphylaxis; however, for unclear reasons, some people with food-specific IgE are asymptomatic upon allergen consumption. We studied strains of mice with different sensitivities to anaphylaxis when orally challenged with allergen to identify possible causes. In resistant C57BL/6 mice, intestinal goblet cells transported less food allergen than did anaphylaxis-susceptible strains, even before allergic sensitization. In a forward genetic screen, resistance was correlated with () variants. DPEP1 is expressed in intestinal epithelium and catabolizes leukotriene D (LTD). Blocking DPEP1 with cilastatin, deleting , or administering LTD orally enhanced allergen transport in resistant mice. Conversely, pretreatment of susceptible mice with a synthesis inhibitor, zileuton, abrogated allergen absorption and oral anaphylaxis, indicating that this could be an approach to treating food allergy.
食物特异性免疫球蛋白E（IgE）会引发危及生命的过敏反应；然而，出于不明原因，一些具有食物特异性IgE的人在食用过敏原后并无症状。我们研究了在口服过敏原激发时对过敏反应具有不同敏感性的小鼠品系，以确定可能的原因。在具有抗性的C57BL/6小鼠中，即使在过敏致敏之前，肠道杯状细胞转运的食物过敏原也比易发生过敏反应的品系少。在一项正向遗传筛选中，抗性与（）变体相关。DPEP1在肠道上皮中表达并分解白三烯D（LTD）。用西司他丁阻断DPEP1、删除或口服LTD可增强抗性小鼠中的过敏原转运。相反，用合成抑制剂齐留通对易感小鼠进行预处理可消除过敏原吸收和口服过敏反应，表明这可能是一种治疗食物过敏的方法。
