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

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 alpha (IL-18R alpha) is a cofactor for immunoglobulin E (IgE) production and Th2 cell development. Studies have not investigated the association between the IL-18/IL-18R alpha signaling pathway and food allergy. Here, we investigated the role of IL-18R alpha in food allergy induction and development. Methods: Wild-type (WT) and IL-18R alpha-null mutant (IL-18R alpha(-)(/-)) 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-18R alpha expression was increased in WT mouse intestines after OVA treatment. Food allergy-induced IL-18R alpha(-/-) 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-18R alpha(-/-) mouse splenocytes than in WT mouse splenocytes. IL18R alpha blockade in WT splenocytes attenuated cell proliferation and Th2 cytokine production. Moreover, STAT3 phosphorylation was reduced in IL-18R alpha(-/-) mice, and SOCS3 and SOCS1 activation were diminished in IL-18R alpha(-/-) intestinal T cells. Conclusions: IL-18R alpha regulates allergic reactions and immune responses by regulating T cell responses in food allergies. Moreover, IL-18R alpha is involved in the STAT/SOCS signaling pathways. Targeting IL-18R alpha signaling might be a novel therapeutic strategy for food allergy.

Automated summary

This study investigated the role of IL-18R alpha in food allergy induction and development. The results showed that IL-18R alpha regulates allergic reactions and immune responses by regulating T cell responses in food allergies. IL-18R alpha is also involved in the STAT/SOCS signaling pathways. Targeting IL-18R alpha signaling might be a novel therapeutic strategy for food allergy.