Immormino Robert M, Smeekens Johanna M, Mathai Priscilla I, Kesselring Janelle R, Turner Andrew V, Kulis Michael D, Moran Timothy P
Department of Pediatrics, UNC School of Medicine, Chapel Hill, NC, United States.
UNC Food Allergy Initiative, Department of Pediatrics, UNC School of Medicine, Chapel Hill, NC, United States.
Front Allergy. 2023 Jul 17;4:1219268. doi: 10.3389/falgy.2023.1219268. eCollection 2023.
Early dietary introduction of peanut has shown efficacy in clinical trials and driven pediatric recommendations for early introduction of peanut to children with heightened allergy risk worldwide. Unfortunately, tolerance is not induced in every case, and a subset of patients are allergic prior to introduction. Here we assess peanut allergic sensitization and oral tolerance in genetically diverse mouse strains.
We aimed to determine whether environmental adjuvant-driven airway sensitization and oral tolerance to peanut could be induced in various genetically diverse mouse strains.
C57BL/6J and 12 Collaborative Cross (CC) mouse strains were fed regular chow or peanut butter to induce tolerance. Tolerance was tested by attempting to sensitize mice via intratracheal exposure to peanut and lipopolysaccharide (LPS), followed by intraperitoneal peanut challenge. Peanut-specific immunoglobulins and peanut-induced anaphylaxis were assessed.
Without oral peanut feeding, most CC strains (11/12) and C57BL/6J induced peanut-specific IgE and IgG1 following airway exposure to peanut and LPS. With oral peanut feeding none of the CC strains nor C57BL/6J mice became sensitized to peanut or experienced anaphylaxis following peanut challenge.
Allergic sensitization and oral tolerance to peanut can be achieved across a range of genetically diverse mice. Notably, the same strains that became allergic via airway sensitization were tolerized by feeding high doses of peanut butter before sensitization, suggesting that the order and route of peanut exposure are critical for determining the allergic fate.
在临床试验中，早期引入花生饮食已显示出疗效，并推动了全球范围内针对过敏风险较高儿童早期引入花生的儿科建议。不幸的是，并非每种情况都能诱导出耐受性，并且一部分患者在引入花生之前就已过敏。在此，我们评估了基因多样化小鼠品系中的花生过敏致敏和口服耐受性。
我们旨在确定在各种基因多样化的小鼠品系中，是否可以通过环境佐剂诱导气道致敏和对花生的口服耐受性。
给C57BL/6J和12个协作杂交（CC）小鼠品系喂食常规饲料或花生酱以诱导耐受性。通过经气管内暴露于花生和脂多糖（LPS）使小鼠致敏，随后进行腹腔内花生激发试验来测试耐受性。评估花生特异性免疫球蛋白和花生诱导的过敏反应。
在未进行花生口服喂养的情况下，大多数CC品系（11/12）和C57BL/6J品系在气道暴露于花生和LPS后诱导产生了花生特异性IgE和IgG1。在进行花生口服喂养后，CC品系和C57BL/6J小鼠均未对花生致敏，也未在花生激发试验后出现过敏反应。
在一系列基因多样化的小鼠中均可实现对花生的过敏致敏和口服耐受性。值得注意的是，那些通过气道致敏而过敏的相同品系，在致敏前通过喂食高剂量花生酱而产生了耐受性，这表明花生暴露的顺序和途径对于决定过敏结局至关重要。
