期刊
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
卷 141, 期 1, 页码 223-+出版社
MOSBY-ELSEVIER
DOI: 10.1016/j.jaci.2017.02.035
关键词
IgE-mediated food allergy; atopic dermatitis; epicutaneous sensitization; T(H)2 polarization; thymic stromal lymphopoietin; basophils; mast cells; IgE; IL-4
资金
- Swiss National Science Foundation [PZ00P3_154777]
- Olga Mayenfisch Stiftung
- Swiss National Science Foundation (SNF) [PZ00P3_154777] Funding Source: Swiss National Science Foundation (SNF)
- Grants-in-Aid for Scientific Research [15H01162, 15H01267] Funding Source: KAKEN
Background: Exaggerated thymic stromal lymphopoietin (TSLP) production and infiltration of basophils are associated with the pathogenesis of atopic dermatitis (AD), a recognized risk factor for the development of food allergies. Although TSLP and basophils have been implicated in promotion of food-induced allergic disorders in response to epicutaneous sensitization, the mechanisms by which TSLP-elicited basophils guide the progression of allergic inflammation in the skin to distant mucosal sites, such as the gastrointestinal tract, are poorly understood. Objective: We sought to test the role of basophil-intrinsic IL-4 production in TH2 sensitization to food antigens in the skin and effector food-induced allergic responses in the gut. Methods: Mice were epicutaneously sensitized with ovalbumin on an AD-like skin lesion, followed by intragastric antigen challenge to induce IgE-mediated food allergy. The requirement for basophil-derived IL-4 production for TH2 polarization and the pathogenesis of IgE-mediated food allergy was assessed in vitro by using coculture experiments with naive T cells and in vivo by using Il4 3'UTR mice that selectively lack IL-4 production in basophils. Results: Epicutaneous food antigen sensitization is associated with infiltration of IL-4-competent innate immune cells to the skin, with basophils and eosinophils representing the predominant populations. In contrast to basophils, absence of eosinophils did not alter disease outcome. Coculture of IL-4-competent basophils together with dendritic cells and naive T cells was sufficient to promote TH2 polarization in an IL-4-dependent manner in vitro, whereas absence of basophil-intrinsic IL-4 production in vivo was associated with reduced food-induced allergic responses. Conclusion: TSLP-elicited basophils promote epicutaneous sensitization to food antigens and subsequent IgE-mediated food allergy through IL-4. Strategies to target the TSLP-basophil-IL-4 axis in patients with AD might lead to innovative therapies that can prevent the progression of allergies to distant mucosal sites.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据