Genetic diversity between mouse strains allows identification of the CC027/GeniUnc strain as an orally reactive model of peanut allergy
Genetic diversity between mouse strains allows identification of the CC027/GeniUnc strain as an orally reactive model of peanut allergy
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DOI：
10.1016/j.jaci.2018.10.009
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发表时间：
2019-03-01
影响因子：
14.2
通讯作者：
Kulis, Michael D.
中科院分区：
文献类型：
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作者：
Orgel, Kelly;Smeekens, Johanna M.;Kulis, Michael D.
背景：需要改进动物模型来了解导致食物过敏的遗传和环境因素。目的：我们试图评估遗传多样性小鼠的食物过敏表型。方法：选取16株CC小鼠及经典近交系C57BL/6J、C3H/HeJ、BALB/cJ进行筛选。先用含或不含霍乱毒素的花生致敏雌性小鼠，再用灌胃或腹腔注射的方式致敏花生，观察其过敏反应。花生特异性免疫球蛋白、T细胞因子、调节性T细胞、肥大细胞和嗜碱性粒细胞被定量。结果：16个CC菌株中有11个对腹腔内花生刺激有过敏反应，而只有CC027/GeniUnc小鼠在口服食物刺激（OFC）后出现了可重复的严重症状。CC027/GeniUnc、C3H/HeJ和C57BL/6J小鼠均对花生产生TH2反应，导致IL-4和IgE的产生，但只有CC027/GeniUnc小鼠对OFC产生反应。口服诱导的CC027/ genunc小鼠的过敏反应与循环中血清Ara h2水平相关，但与过敏原特异性IgE或粘膜肥大细胞蛋白酶1水平无关，表明全身过敏原吸收对通过胃肠道的过敏反应很重要。此外，CC027/GeniUnc，而不是C3H/HeJ或BALB/cJ，可以使小鼠在没有霍乱毒素的情况下致敏，并在OFC上对花生产生反应。结论：我们已经确定并鉴定了CC027/GeniUnc小鼠是一种对花生过敏易感的遗传菌株，并且在OFC后容易发生严重的反应。更广泛地说，这些发现证明了CC人群在开发过敏研究新模型方面尚未开发的潜力。
Background: Improved animal models are needed to understand the genetic and environmental factors that contribute to food allergy.Objective: We sought to assess food allergy phenotypes in a genetically diverse collection of mice.Methods: We selected 16 Collaborative Cross (CC) mouse strains, as well as the classic inbred C57BL/6J, C3H/HeJ, and BALB/cJ strains, for screening. Female mice were sensitized to peanut intragastrically with or without cholera toxin and then challenged with peanut by means of oral gavage or intraperitoneal injection and assessed for anaphylaxis. Peanut-specific immunoglobulins, T-cell cytokines, regulatory T cells, mast cells, and basophils were quantified.Results: Eleven of the 16 CC strains had allergic reactions to intraperitoneal peanut challenge, whereas only CC027/GeniUnc mice reproducibly experienced severe symptoms after oral food challenge (OFC). CC027/GeniUnc, C3H/HeJ, and C57BL/6J mice all mounted a TH2 response against peanut, leading to production of IL-4 and IgE, but only the CC027/GeniUnc mice reacted to OFC. Orally induced anaphylaxis in CC027/GeniUnc mice was correlated with serum levels of Ara h 2 in circulation but not with allergen-specific IgE or mucosal mast cell protease 1 levels, indicating systemic allergen absorption is important for anaphylaxis through the gastrointestinal tract. Furthermore, CC027/GeniUnc, but not C3H/HeJ or BALB/cJ, mice can be sensitized in the absence of cholera toxin and react on OFC to peanut.Conclusions: We have identified and characterized CC027/GeniUnc mice as a strain that is genetically susceptible to peanut allergy and prone to severe reactions after OFC. More broadly, these findings demonstrate the untapped potential of the CC population in developing novel models for allergy research.