The role of basophils and proallergic cytokines, TSLP and IL-33, in cutaneously sensitized food allergy

The role of basophils and proallergic cytokines, TSLP and IL-33, in cutaneously sensitized food allergy
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DOI:
10.1093/intimm/dxu058
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发表时间:
2014-10-01
影响因子:
4.4
通讯作者:
Yoshimoto, Tomohiro
Yoshimoto, Tomohiro
中科院分区:
医学3区
文献类型:
--
作者:
Muto, Taichiro;Fukuoka, Ayumi;Yoshimoto, Tomohiro

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食物抗原在食用前的皮肤致敏引起食物过敏的发展。在这里,我们报告了嗜碱性粒细胞和过敏前细胞因子、胸腺基质淋巴生成素(TSLP)和IL-33在食物过敏小鼠模型中的部位和阶段依赖性作用,这些模型最初是由食物抗原致敏的。小鼠外源性食物抗原卵清蛋白(OVA)致敏,然后口服OVA。表皮致敏小鼠在口服刺激后产生ova特异性IgE并发生IgE依赖性过敏反应。嗜碱性粒细胞减少或tslp受体缺乏的小鼠不产生ova特异性IgE,并且免受口腔攻击诱导的过敏反应的保护。il -33缺失小鼠产生正常水平的ova特异性IgE。然而,IL-33缺陷小鼠和重组可溶性IL-33受体处理的小鼠对过敏反应有保护作用。因此,嗜碱性粒细胞和TSLP在食物过敏致敏阶段皮肤T(h)2的发育中起关键作用。相比之下,虽然IL-33在促进皮肤抗原致敏中是必不可少的,但这种细胞因子对于诱导肠道中ige依赖性过敏反应是必不可少的。
Cutaneous sensitization with a food antigen before its consumption elicits the development of food allergy. Here, we report the site- and stage-dependent roles of basophils and proallergic cytokines, thymic stromal lymphopoietin (TSLP) and IL-33, in a mouse model of food allergy initially sensitized cutaneously with the food antigen. Mice were epicutaneously sensitized with the food antigen ovalbumin (OVA) followed by oral challenge with OVA. Epicutaneously sensitized mice produced OVA-specific IgE and developed IgE-dependent anaphylaxis after oral challenge. Basophil-depleted or TSLP-receptor-deficient mice did not produce OVA-specific IgE and were protected from oral challenge-induced anaphylaxis. IL-33-deficient mice produced normal levels of OVA-specific IgE. However, IL-33-deficient mice and mice treated with recombinant soluble IL-33 receptor were protected from anaphylaxis. Thus, basophils and TSLP have pivotal roles in T(h)2 development in the skin during the sensitization phase of food allergy. In contrast, while IL-33 is dispensable for promoting cutaneous antigen sensitization, the cytokine is essential for inducing IgE-dependent anaphylaxis in the gut.