Allergic sensitization can be induced via multiple physiologic routes in an adjuvant-dependent manner.
Allergic sensitization can be induced via multiple physiologic routes in an adjuvant-dependent manner.
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DOI：
10.1016/j.jaci.2011.06.007
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发表时间：
2011-12
期刊：
影响因子：
--
通讯作者：
Mayer L
中科院分区：
文献类型：
--
作者：
Dunkin D;Berin MC;Mayer L
口腔接触食物过敏原在婴儿期可能是有限的，抗原接触的初始部位可能在食物过敏诱导中起重要作用。检查不同途径使用牛奶过敏原，有和没有佐剂，对致敏的影响。C3H/HeJ小鼠反复暴露于牛奶过敏原α-乳清蛋白（ALA），伴或不伴霍乱毒素（CT）。使用的致敏途径有胃内、皮肤、鼻内和舌下。过敏反应的严重程度是通过对口服或全身刺激的症状和体温来评估的。ELISA法检测血清抗原特异性抗体。同时确定了皮肤CT辅助作用的机制。通过过敏原特异性IgE测量的ALA致敏发生在所有致敏途径中，并且对皮肤暴露的反应最大。致敏作用依赖于CT，而不是通过任何途径单独对抗原发生。粘膜暴露，而非皮肤暴露，导致强烈的过敏原特异性IgA反应。所有致敏组口服ALA时均发生过敏反应。局部CT诱导兰格林阴性真皮dc向淋巴结迁移，导致反应性T细胞增殖和Th2细胞因子产生增强。当佐剂存在时，致敏可通过所有生理途径发生。皮肤是致敏的有效且可能重要的生理途径，佐剂诱导携带抗原的真皮dc向淋巴结流出，产生促过敏Th2反应。
Oral exposure to food allergens may be limited in infancy and the initial site of antigen exposure likely plays an important role in food allergy induction. To examine the impact of different routes of exposure using milk allergens, with and without adjuvant, on sensitization. C3H/HeJ mice were repeatedly exposed to the milk allergen α-lactalbumin (ALA), with or without cholera toxin (CT). Sensitization routes used were intragastric, cutaneous, intranasal, and sublingual. Anaphylaxis severity was assessed by symptoms and body temperature in response to oral or systemic challenge. Antigen-specific serum antibodies were measured by ELISA. The mechanism of adjuvant activity of cutaneous CT was also determined. Sensitization to ALA as measured by allergen-specific IgE occurred by all routes of sensitization, and was maximal in response to cutaneous exposure. Sensitization was dependent on CT and did not occur to antigen alone by any route. Mucosal, but not cutaneous exposure, resulted in a robust allergen-specific IgA response. Anaphylaxis occurred in all sensitized groups when orally challenged with ALA. Topical CT induced migration of langerinneg dermal DCs to the lymph node, resulting in enhanced proliferation and Th2 cytokine production from responder T cells. Sensitization can occur via all physiologic routes when adjuvant is present. The skin is a potent and likely important physiologic route of sensitization whereby adjuvant induces an efflux of antigen-bearing dermal DCs to the lymph node that generate a pro-allergic Th2 response.
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