白细胞介素-4 受体 α 信号转导改变了小鼠的口服食物挑战和免疫治疗结果。
IL-4 receptor alpha signaling alters oral food challenge and immunotherapy outcomes in mice.
机构信息
Mary H. Weiser Food Allergy Center, University of Michigan, Ann Arbor, Mich.
Mary H. Weiser Food Allergy Center, University of Michigan, Ann Arbor, Mich; Division of Allergy and Immunology, University of Michigan, Ann Arbor, Mich.
出版信息
J Allergy Clin Immunol. 2023 Jan;151(1):182-191.e6. doi: 10.1016/j.jaci.2022.07.011. Epub 2022 Aug 4.
BACKGROUND
Food allergy diagnosis and management causes a number of social and emotional challenges for individuals with food allergies and their caregivers. This has led to increased interest in developing approaches to accurately predict food allergy diagnosis, severity of food allergic reactions, and treatment outcomes. However, the utility of these approaches is somewhat conflicting.
OBJECTIVE
We sought to develop and utilize a murine model that mimics the disease course of food allergy diagnosis and treatment in humans and to identify biomarkers that predict reactivity during food challenge (FC) and responsiveness during oral immunotherapy (OIT) and how these outcomes are modified by genetics.
METHODS
Skin-sensitized intestinal IL-9 transgenic (IL9Tg) and IL9Tg mice backcrossed onto the IL-4Rα background received a single intragastric exposure of egg antigen (ovalbumin), underwent oral FC and OIT; food allergy severity, mast cell activation, and ovalbumin-specific IgE levels were examined to determine the predictability of these outcomes in determining reactivity and treatment outcomes.
RESULTS
Subcutaneous sensitization and a single intragastric allergen challenge of egg antigen to BALB/c IL9Tg mice and Il4ra IL9Tg induced a food allergic reaction. Enhanced IL-4Rα signaling altered the symptoms induced by the first oral exposure, decreased the cumulative antigen dose, increased the severity of reaction during oral FC, and altered the frequency of adverse events and OIT outcomes. Biomarkers after first oral exposure indicated that only the severity of the initial reaction significantly correlated with cumulative dose of oral FC.
CONCLUSION
Collectively, these data indicate that single nucleotide polymorphisms in IL-4Rα can alter clinical symptoms of food allergic reactions, severity, and reactive dose during FC and OIT, and that severity of first reaction can predict the likelihood of reaction during FC in mice with IL-4Rα gain of function.
背景
食物过敏的诊断和管理给食物过敏患者及其照顾者带来了许多社交和情绪方面的挑战。这导致人们越来越感兴趣开发方法来准确预测食物过敏的诊断、食物过敏反应的严重程度和治疗结果。然而，这些方法的实用性存在一些矛盾。
目的
我们试图开发并利用一种模拟人类食物过敏诊断和治疗过程的小鼠模型，并确定预测食物挑战（FC）期间反应性和口服免疫治疗（OIT）期间反应性的生物标志物，以及这些结果如何受遗传因素的影响。
方法
皮肤致敏的肠道 IL-9 转基因（IL9Tg）和 IL9Tg 小鼠与 IL-4Rα 背景回交，接受单次胃内卵抗原（卵清蛋白）暴露，进行口服 FC 和 OIT；检查食物过敏严重程度、肥大细胞活化和卵清蛋白特异性 IgE 水平，以确定这些结果在预测反应性和治疗结果方面的可预测性。
结果
皮下致敏和单次胃内卵抗原致敏 BALB/c IL9Tg 小鼠和 Il4ra IL9Tg 诱导食物过敏反应。增强的 IL-4Rα 信号改变了第一次口服暴露诱导的症状，减少了累积抗原剂量，增加了口服 FC 期间反应的严重程度，并改变了不良反应和 OIT 结果的频率。第一次口服暴露后的生物标志物表明，只有初始反应的严重程度与口服 FC 的累积剂量显著相关。
结论
综上所述，这些数据表明 IL-4Rα 的单核苷酸多态性可以改变食物过敏反应、严重程度和 FC 和 OIT 期间的反应性剂量，并且 IL-4Rα 功能获得的小鼠中第一次反应的严重程度可以预测 FC 期间反应的可能性。
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