IL-4 production by group 2 innate lymphoid cells promotes food allergy by blocking regulatory T-cell function

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:138

Article

Noval Rivas, Magali^1,2,3  Burton, Oliver T.^1,2  Oettgen, Hans C.^1,2  Chatila, Talal^1,2 

[1] Boston Childrens Hosp, Div Immunol, Karp Family Bldg,Rm 10-214,1 Blackfan St, Boston, MA 02115 USA

[2] Harvard Med Sch, Dept Pediat, Karp Family Bldg,Rm 10-214,1 Blackfan St, Boston, MA 02115 USA

[3] Cedars Sinai Med Ctr, Dept Pediat, Div Pediat Infect Dis & Immunol, Infect & Immunol Dis Res Ctr, Los Angeles, CA 90048 USA

关键词: Anaphylaxis;    food allergy;    IL-4;    IL-13;    IL-33;    group 2 innate lymphoid cells;    innate lymphoid cells;    nuocytes;    mast cells;    regulatory T cells;    oral tolerance;   

DOI  :  10.1016/j.jaci.2016.02.030

来源: Elsevier

【 摘 要 】

Background: Food allergy is a major health issue, but its pathogenesis remains obscure. Group 2 innate lymphoid cells (ILC2s) promote allergic inflammation. However their role in food allergy is largely unknown. Objective: We sought to investigate the role of ILC2s in food allergy. Methods: Food allergy-prone mice with a gain-of-function mutation in the IL-4 receptor a chain (Il4raF709) were orally sensitized with food allergens, and the ILC2 compartment was analyzed. The requirement for ILC2s in food allergy was investigated by using Il4raF709, IL-33 receptor-deficient (Il1rl1(-/-)), IL-13-deficient (Il13(-/-)), and IL-4-deficient (Il4(-/-)) mice and by adoptive transfer of in vitro-expanded ILC2s. Direct effects of ILC2s on regulatory T (Treg) cells and mast cells were analyzed in coculture experiments. Treg cell control of ILC2s was assessed in vitro and in vivo. Results: Il4raF709 mice with food allergy exhibit increased numbers of ILC2s. IL-4 secretion by ILC2s contributes to the allergic response by reducing allergen-specific Treg cell and activating mast cell counts. IL-33 receptor deficiency in Il4raF709 Il1rl1(-/-) mice protects against allergen sensitization and anaphylaxis while reducing ILC2 induction. Adoptive transfer of wild-type and Il13(-/-) but not Il4(-/-) ILC2s restored sensitization in Il4raF709 Il1rl1(-/-) mice. Treg cells suppress ILC2s in vitro and in vivo. Conclusion: IL-4 production by IL-33-stimulated ILC2s blocks the generation of allergen-specific Treg cells and favors food allergy. Strategies to block ILC2 activation or the IL-33/IL-33 receptor pathway can lead to innovative therapies in the treatment of food allergy.

【 授权许可】

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