Allergen-specific IgG antibody signaling through FcγRIIb promotes food tolerance.
Allergen-specific IgG antibody signaling through FcγRIIb promotes food tolerance.
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DOI：
10.1016/j.jaci.2017.03.045
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发表时间：
2018-01
期刊：
影响因子：
--
通讯作者：
Oettgen HC
中科院分区：
文献类型：
--
作者：
Burton OT;Tamayo JM;Stranks AJ;Koleoglou KJ;Oettgen HC
食物过敏受试者产生高滴度IgE抗体，通过FcεRI与肥大细胞结合，并在遇到抗原时引发速发型超敏反应。食物特异性IgG抗体在自然解决食物过敏的情况下产生，并伴随着在口服免疫疗法（OIT）中获得食物过敏原无反应性。在本研究中，我们试图描述IgG及其抑制性Fc受体FcγRIIb对未处理动物的从头过敏原致敏作用以及对既存食物过敏背景下已建立的免疫应答的影响。将过敏原特异性IgG给予经历对模型食物过敏原卵清蛋白（OVA）的致敏和脱敏的小鼠。使用肥大细胞和Fcγ RIIb缺陷小鼠研究细胞和分子机制。使用中和抗体研究IgG介导的人肥大细胞抑制中FcγRII的需求。在初始食物暴露期间向食物过敏易感性IL4raF709小鼠施用特异性IgG防止了激发后IgE抗体、辅助性T细胞（Th）2应答和过敏性应答的发展。当在具有IgE介导的超敏反应的小鼠中作为口服脱敏的辅助给药时，IgG促进耐受性恢复，有利于Foxp3+调节性T细胞（Treg）的扩增，沿着抑制现有的Th2和IgE应答。IgG和FcγRIIb通过影响肥大细胞功能抑制适应性变态反应。这些发现表明，过敏原特异性IgG抗体可以诱导和维持对食物的免疫耐受。
Food-allergic subjects produce high-titer IgE antibodies that bind to mast cells via FcεRI and trigger immediate hypersensitivity reactions upon antigen encounter. Food-specific IgG antibodies arise in the setting of naturally resolving food allergy and accompany the acquisition of food allergen unresponsiveness in oral immunotherapy (OIT). In this study, we sought to delineate the effects of IgG and its inhibitory Fc receptor, FcγRIIb, on both de novo allergen sensitization in naïve animals and on established immune responses in the setting of pre-existing food allergy. Allergen-specific IgG was administered to mice undergoing sensitization and desensitization to the model food allergen, ovalbumin (OVA). Cellular and molecular mechanisms were interrogated using mast cell- and FcγRIIb-deficient mice. The requirement for FcγRII in IgG-mediated inhibition of human mast cells was investigated using a neutralizing antibody. Administration of specific IgG to food allergy-prone IL4raF709 mice during initial food exposure prevented the development of IgE antibodies, T helper (Th) 2 responses, and anaphylactic responses upon challenge. When given as an adjunct to oral desensitization in mice with established IgE-mediated hypersensitivity, IgG facilitated tolerance restoration, favoring the expansion of Foxp3+ regulatory T cells (Treg) along with suppression of existing Th2 and IgE responses. IgG and FcγRIIb suppresses the adaptive allergic responses via effects on mast cell function. These findings suggest that allergen-specific IgG antibodies can act to induce and sustain immunological tolerance to foods.
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