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

Allergy Asthma Immunol Res. 2022 Jul;14(4):424-438. English. https://doi.org/10.4168/aair.2022.14.4.424

Eun Gyul Kim, Ji Su Leem, Seung Min Baek, Hye Rin Kim, Kyung Won Kim, Mi Na Kim, and Myung Hyun Sohn

Abstract

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. PDF