Basophil-derived IL-4 promotes epicutaneous antigen sensitization concomitant with the development of food allergy

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:141

Article

Hussain, Maryam^1,2  Borcard, Loic¹  Walsh, Kevin P.³  Rodriguez, Maria Pena¹  Mueller, Christoph¹  Kim, Brian S.⁴  Kubo, Masato⁵  Artis, David⁶  Noti, Mario¹ 

[1] Univ Bern, Inst Pathol, Div Expt Pathol, CH-3008 Bern, Switzerland

[2] Univ Bern, Grad Sch Cellular & Biomed Sci, Bern, Switzerland

[3] Univ Penn, Dept Microbiol, Perelman Sch Med, Philadelphia, PA 19104 USA

[4] Washington Univ, Sch Med, Dept Med, Div Dermatol, St Louis, MO 63110 USA

[5] Tokyo Univ Sci, Div Mol Pathol, Res Inst Biomed Sci, RIKEN,Ctr Integrat Med Sci IMS,Yokohama Inst,Lab, Noda, Chiba, Japan

[6] Cornell Univ, Dept Microbiol & Immunol, Weill Cornell Med Coll, Jill Roberts Inst Res Inflammatory Bowel Dis,Joan, Ithaca, NY 14853 USA

关键词: IgE-mediated food allergy;    atopic dermatitis;    epicutaneous sensitization;    T(H)2 polarization;    thymic stromal lymphopoietin;    basophils;    mast cells;    IgE;    IL-4;   

DOI  :  10.1016/j.jaci.2017.02.035

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

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