PMID- 35837825 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220721 IS - 2092-7355 (Print) IS - 2092-7363 (Electronic) IS - 2092-7355 (Linking) VI - 14 IP - 4 DP - 2022 Jul TI - Interleukin-18 Receptor alpha Modulates the T Cell Response in Food Allergy. PG - 424-438 LID - 10.4168/aair.2022.14.4.424 [doi] AB - 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-18Ralpha) is a cofactor for immunoglobulin E (IgE) production and Th2 cell development. Studies have not investigated the association between the IL-18/IL-18Ralpha signaling pathway and food allergy. Here, we investigated the role of IL-18Ralpha in food allergy induction and development. METHODS: Wild-type (WT) and IL-18Ralpha-null mutant (IL-18Ralpha(-/-)) 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-18Ralpha expression was increased in WT mouse intestines after OVA treatment. Food allergy-induced IL-18Ralpha(-/-) 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-18Ralpha(-/-) mouse splenocytes than in WT mouse splenocytes. IL-18Ralpha blockade in WT splenocytes attenuated cell proliferation and Th2 cytokine production. Moreover, STAT3 phosphorylation was reduced in IL-18Ralpha(-/-) mice, and SOCS3 and SOCS1 activation were diminished in IL-18Ralpha(-/-) intestinal T cells. CONCLUSIONS: IL-18Ralpha regulates allergic reactions and immune responses by regulating T cell responses in food allergies. Moreover, IL-18Ralpha is involved in the STAT/SOCS signaling pathways. Targeting IL-18Ralpha signaling might be a novel therapeutic strategy for food allergy. CI - Copyright (c) 2022 The Korean Academy of Asthma, Allergy and Clinical Immunology * The Korean Academy of Pediatric Allergy and Respiratory Disease. FAU - Kim, Eun Gyul AU - Kim EG AUID- ORCID: 0000-0002-2546-9919 AD - Department of Pediatrics, Severance Hospital, Institute of Allergy, Institute for Immunology and Immunological Diseases, Severance Biomedical Science Institute, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul, Korea. FAU - Leem, Ji Su AU - Leem JS AUID- ORCID: 0000-0002-7308-1978 AD - Department of Pediatrics, Severance Hospital, Institute of Allergy, Institute for Immunology and Immunological Diseases, Severance Biomedical Science Institute, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul, Korea. FAU - Baek, Seung Min AU - Baek SM AUID- ORCID: 0000-0001-5146-8605 AD - Department of Pediatrics, Severance Hospital, Institute of Allergy, Institute for Immunology and Immunological Diseases, Severance Biomedical Science Institute, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul, Korea. FAU - Kim, Hye Rin AU - Kim HR AUID- ORCID: 0000-0002-2783-9127 AD - Department of Pediatrics, Severance Hospital, Institute of Allergy, Institute for Immunology and Immunological Diseases, Severance Biomedical Science Institute, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul, Korea. FAU - Kim, Kyung Won AU - Kim KW AUID- ORCID: 0000-0003-4529-6135 AD - Department of Pediatrics, Severance Hospital, Institute of Allergy, Institute for Immunology and Immunological Diseases, Severance Biomedical Science Institute, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul, Korea. FAU - Kim, Mi Na AU - Kim MN AUID- ORCID: 0000-0002-1675-0688 AD - Department of Pediatrics, Severance Hospital, Institute of Allergy, Institute for Immunology and Immunological Diseases, Severance Biomedical Science Institute, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul, Korea. SKDIAALSK@yuhs.ac. FAU - Sohn, Myung Hyun AU - Sohn MH AUID- ORCID: 0000-0002-2478-487X AD - Department of Pediatrics, Severance Hospital, Institute of Allergy, Institute for Immunology and Immunological Diseases, Severance Biomedical Science Institute, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul, Korea. mhsohn@yuhs.ac. LA - eng GR - NRF-2020R1A2B5B02001713/National Research Foundation of Korea/Korea GR - NRF-2018R1A5A2025079/National Research Foundation of Korea/Korea GR - NRF-2021R1I1A1A01049002/National Research Foundation of Korea/Korea PT - Journal Article PL - Korea (South) TA - Allergy Asthma Immunol Res JT - Allergy, asthma & immunology research JID - 101518382 PMC - PMC9293601 OTO - NOTNLM OT - Food allergy OT - STAT3 Transcription Factor OT - Th2 cells OT - interleukin-18 OT - pathophysiology OT - receptors OT - suppressors of cytokine signaling proteins COIS- There are no financial or other issues that might lead to a conflict of interest. EDAT- 2022/07/16 06:00 MHDA- 2022/07/16 06:01 PMCR- 2022/07/01 CRDT- 2022/07/15 04:03 PHST- 2022/03/07 00:00 [received] PHST- 2022/04/28 00:00 [revised] PHST- 2022/05/07 00:00 [accepted] PHST- 2022/07/15 04:03 [entrez] PHST- 2022/07/16 06:00 [pubmed] PHST- 2022/07/16 06:01 [medline] PHST- 2022/07/01 00:00 [pmc-release] AID - 14.424 [pii] AID - 10.4168/aair.2022.14.4.424 [doi] PST - ppublish SO - Allergy Asthma Immunol Res. 2022 Jul;14(4):424-438. doi: 10.4168/aair.2022.14.4.424.