Prevention of food allergy development and suppression of established food allergy by neutralization of thymic stromal lymphopoietin, IL-25, and IL-33

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:141

Article

Khodoun, Marat V.^1,2  Tomar, Sunil⁵  Tocker, Joel E.⁴  Wang, Yui Hsi⁵  Finkelman, Fred D.^1,3,6 

[1] Univ Cincinnati, Coll Med, Dept Internal Med, Div Allergy Immunol & Rheumatol, Cincinnati, OH 45267 USA

[2] Cincinnati Dept Vet Affairs Med Ctr, Dept Res, Cincinnati, OH USA

[3] Cincinnati Dept Vet Affairs Med Ctr, Dept Med, Cincinnati, OH USA

[4] Inflammat Res Assoc, Narberth, Wales

[5] Cincinnati Childrens Hosp, Med Ctr, Div Allergy & Clin Immunol, Cincinnati, OH USA

[6] Cincinnati Childrens Hosp, Med Ctr, Div Immunobiol, Cincinnati, OH USA

关键词: Anaphylaxis;    antibodies;    cytokines;    food allergy;    mice;    treatment;    triglycerides;   

DOI  :  10.1016/j.jaci.2017.02.046

来源: Elsevier

【 摘 要 】

Background: Food allergy (FA) is an increasing problem that has no approved treatment. The pro-T(H)2 cytokines IL-25, IL-33, and thymic stromal lymphopoietin (TSLP) are associated with FA, and mAbs to these cytokines are reported to suppress murine FA development. Objective: We sought to determine whether anti-pro-T(H)2 cytokine mAbs can block both FA maintenance and induction. Methods: IgE-mediated FA was induced in BALB/c mice by oral gavage with medium-chain triglycerides (MCTs) plus egg white (EW) and was characterized by increased numbers of lamina propria T(H)2 cells, mast cells, and eosinophils, shock (hypothermia), mast cell degranulation (increased serum mouse mast cell protease 1), increased serum IgG1 anti-EW and IgE levels, and increased IL-4 and IL-13 secretion after MCT/EW challenge. Mice were injected with anti-IL-25, IL-33 receptor, and/or TSLP mAbs before initial oral gavage with MCT/EW to suppress FA development; treatment with the same mAbs was initiated after FA development to suppress established FA. Results: Injection of an mAb to IL-25, IL-33 receptor, or TSLP strongly inhibited FA development. No single mAb to a pro-T(H)2 cytokine could suppress established FA, and optimal FA suppression required treatment with a cocktail of all 3 anti-proT(H)2 mAbs. Treatment with the 3-mAb cocktail during initial MCT/EW immunization induced EW tolerance. Conclusion: All of the pro-T(H)2 cytokines are required to induce our model of FA, whereas any pro-T(H)2 cytokine can maintain established FA. Pro-T(H)2 cytokines prevent oral tolerance. Combined treatment with antagonists to all 3 pro-T(H)2 cytokines or with an inhibitor of pro-T(H)2 cytokine production might be able to suppress established human FA.

【 授权许可】

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