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

Allergy, Asthma & Immunology Research

Kim, EG;Leem, JS;Baek, SM;Kim, HR;Kim, KW;Kim, MN;Sohn, MH;

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.

PubMed ID: 35837825

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