Strid J, Hourihane J, Kimber I, Callard R, Strobel S
Immunobiology Unit, Institute of Child Health, University College London, London, UK.
Clin Exp Allergy. 2005 Jun;35(6):757-66. doi: 10.1111/j.1365-2222.2005.02260.x.
Food allergies are an important cause of life-threatening hypersensitivity reactions. Oral tolerance can be considered the default immune response to dietary antigens, with immune deviation resulting in allergic sensitization. However, primary sensitization to food allergens may not solely be through the gastrointestinal mucosa, as strong T-helper type 2 (Th2)-biased immunity can result from exposure to protein allergens on barrier-disrupted skin.
The purpose of this study was to examine whether exposure to allergens through the skin may interfere with the normal development of oral tolerance and promote allergic sensitization to food proteins.
Female BALB/c mice were exposed epicutaneously to peanut protein and induction of systemic oral tolerance through high dose feeds of peanut protein was subsequently assessed. Other mice were rendered tolerant prior to epicutaneous peanut exposure. Sensitivity to peanut was determined by assessing delayed-type hypersensitivity, proliferative, cytokine and antibody responses.
Epicutaneous exposure to peanut protein induced potent Th2-type immunity with high levels of IL-4 and serum IgE. Primary skin exposure prevented the subsequent induction of oral tolerance to peanut in an antigen-specific manner. Upon oral challenge, mice became further sensitized and developed strong peanut-specific IL-4 and IgE responses. Furthermore, animals with existing tolerance to peanut were partly sensitized following epicutaneous exposure.
Epicutaneous exposure to peanut protein can prevent induction of oral tolerance, and may even modify existing tolerance to peanut. Epidermal exposure to protein allergens selectively drives Th2-type responses, and as such may promote sensitization to food proteins upon gastrointestinal exposure.
食物过敏是危及生命的超敏反应的重要原因。口服耐受可被视为对饮食抗原的默认免疫反应，而免疫偏离会导致过敏致敏。然而，对食物过敏原的初次致敏可能并非仅通过胃肠道黏膜，因为暴露于屏障受损皮肤上的蛋白质过敏原可导致强烈的2型辅助性T细胞（Th2）偏向性免疫。
本研究的目的是检验通过皮肤接触过敏原是否会干扰口服耐受的正常发育，并促进对食物蛋白的过敏致敏。
对雌性BALB/c小鼠进行经皮花生蛋白暴露，随后评估通过高剂量喂食花生蛋白诱导全身口服耐受的情况。其他小鼠在经皮花生暴露前已建立耐受。通过评估迟发型超敏反应、增殖反应、细胞因子和抗体反应来确定对花生的敏感性。
经皮暴露于花生蛋白可诱导产生具有高水平白细胞介素-4（IL-4）和血清免疫球蛋白E（IgE）的强效Th2型免疫。初次皮肤暴露以抗原特异性方式阻止了随后对花生口服耐受的诱导。经口服激发后，小鼠进一步致敏并产生强烈的花生特异性IL-4和IgE反应。此外，对花生已具有耐受性的动物在经皮暴露后部分致敏。
经皮暴露于花生蛋白可阻止口服耐受的诱导，甚至可能改变对花生已有的耐受性。表皮暴露于蛋白质过敏原选择性地驱动Th2型反应，因此可能促进胃肠道暴露时对食物蛋白的致敏。
