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Interleukin-18 Receptor α Modulates the T Cell Response in Food Allergy

 Eun Gyul Kim  ;  Ji Su Leem  ;  Seung Min Baek  ;  Hye Rin Kim  ;  Kyung Won Kim  ;  Mi Na Kim  ;  Myung Hyun Sohn 
 ALLERGY ASTHMA & IMMUNOLOGY RESEARCH, Vol.14(4) : 424-438, 2022-07 
Journal Title
Issue Date
Food allergy ; STAT3 Transcription Factor ; Th2 cells ; interleukin-18 ; pathophysiology ; receptors ; suppressors of cytokine signaling proteins
Purpose: The prevalence of food allergy, triggered by T-helper type 2 (Th2) cell-mediated inflammation, is increasing worldwide. Interleukin (IL)-18 plays an important role in inflammatory diseases by binding with the IL-18 receptor. IL-18/IL-18 receptor α (IL-18Rα) is a cofactor for immunoglobulin E (IgE) production and Th2 cell development. Studies have not investigated the association between the IL-18/IL-18Rα signaling pathway and food allergy. Here, we investigated the role of IL-18Rα in food allergy induction and development.

Methods: Wild-type (WT) and IL-18Rα-null mutant (IL-18Rα-/-) C57BL/6 mice were sensitized and challenged using ovalbumin (OVA) for food allergy induction. Food allergy symptoms, T cell-mediated immune responses, and signal transducer and activator of transcription (STAT)/suppressors of cytokine signaling (SOCS) pathways were analyzed in mice.

Results: IL-18Rα expression was increased in WT mouse intestines after OVA treatment. Food allergy-induced IL-18Rα-/- mice showed attenuated systemic food allergic reactions, OVA-specific IgE and mouse mast cell protease-1 production, inflammatory cell infiltration, and T cell activation. Ex vivo experiments showed that cell proliferation and Th2 cytokine production were lower in IL-18Rα-/- mouse splenocytes than in WT mouse splenocytes. IL-18Rα blockade in WT splenocytes attenuated cell proliferation and Th2 cytokine production. Moreover, STAT3 phosphorylation was reduced in IL-18Rα-/- mice, and SOCS3 and SOCS1 activation were diminished in IL-18Rα-/- intestinal T cells.

Conclusions: IL-18Rα regulates allergic reactions and immune responses by regulating T cell responses in food allergies. Moreover, IL-18Rα is involved in the STAT/SOCS signaling pathways. Targeting IL-18Rα signaling might be a novel therapeutic strategy for food allergy.
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1. College of Medicine (의과대학) > Dept. of Pediatrics (소아과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Kyung Won(김경원) ORCID logo https://orcid.org/0000-0003-4529-6135
Sohn, Myung Hyun(손명현) ORCID logo https://orcid.org/0000-0002-2478-487X
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