Orally desensitized mast cells form a regulatory network with Treg cells for the control of food allergy.

Autor: Takasato Y; Department of Mucosal Immunology, The University of Tokyo Distinguished Professor Unit, The Institute of Medical Science, The University of Tokyo, Tokyo, 108-8639, Japan.; Department of Pediatrics, Keio University School of Medicine, Tokyo, 160-8582, Japan., Kurashima Y; Department of Mucosal Immunology, The University of Tokyo Distinguished Professor Unit, The Institute of Medical Science, The University of Tokyo, Tokyo, 108-8639, Japan. yosukek@ims.u-tokyo.ac.jp.; Department of Innovative Medicine and Mucosal Immunology, Graduate School of Medicine, Chiba University, Chiba, 260-8670, Japan. yosukek@ims.u-tokyo.ac.jp.; International Research and Development Center for Mucosal Vaccines, The Institute of Medical Science, The University of Tokyo, Tokyo, 108-8639, Japan. yosukek@ims.u-tokyo.ac.jp.; Division of Gastroenterology, Department of Medicine, CU-UCSD Center for Mucosal Immunology, Allergy and Vaccines (CU-UCSD cMAV), University of California, San Diego, CA, 92093-0956, USA. yosukek@ims.u-tokyo.ac.jp.; Institute for Global Prominent Research, Chiba University, Chiba, 260-8670, Japan. yosukek@ims.u-tokyo.ac.jp.; Laboratory of Vaccine Materials, Center for Vaccine and Adjuvant Research and Laboratory of Gut Environmental System, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka, 567-0085, Japan. yosukek@ims.u-tokyo.ac.jp., Kiuchi M; Department of Immunology, Graduate School of Medicine, Chiba University, Chiba, 260-8670, Japan., Hirahara K; Department of Immunology, Graduate School of Medicine, Chiba University, Chiba, 260-8670, Japan., Murasaki S; Department of Mucosal Immunology, The University of Tokyo Distinguished Professor Unit, The Institute of Medical Science, The University of Tokyo, Tokyo, 108-8639, Japan.; International Research and Development Center for Mucosal Vaccines, The Institute of Medical Science, The University of Tokyo, Tokyo, 108-8639, Japan., Arai F; Department of Mucosal Immunology, The University of Tokyo Distinguished Professor Unit, The Institute of Medical Science, The University of Tokyo, Tokyo, 108-8639, Japan.; International Research and Development Center for Mucosal Vaccines, The Institute of Medical Science, The University of Tokyo, Tokyo, 108-8639, Japan., Izawa K; Atopy Research Center, Juntendo University Graduate School of Medicine, Tokyo, 113-8421, Japan., Kaitani A; Atopy Research Center, Juntendo University Graduate School of Medicine, Tokyo, 113-8421, Japan., Shimada K; Department of Mucosal Immunology, The University of Tokyo Distinguished Professor Unit, The Institute of Medical Science, The University of Tokyo, Tokyo, 108-8639, Japan.; International Research and Development Center for Mucosal Vaccines, The Institute of Medical Science, The University of Tokyo, Tokyo, 108-8639, Japan., Saito Y; Department of Innovative Medicine and Mucosal Immunology, Graduate School of Medicine, Chiba University, Chiba, 260-8670, Japan., Toyoshima S; Allergy and Immunology Research Project Team, Research Institute of Medical Science, Center for Allergy, Center for Medical Education, Nihon University School of Medicine, Tokyo, 173-8610, Japan., Nakamura M; Department of Mucosal Immunology, The University of Tokyo Distinguished Professor Unit, The Institute of Medical Science, The University of Tokyo, Tokyo, 108-8639, Japan., Fujisawa K; Department of Mucosal Immunology, The University of Tokyo Distinguished Professor Unit, The Institute of Medical Science, The University of Tokyo, Tokyo, 108-8639, Japan., Okayama Y; Allergy and Immunology Research Project Team, Research Institute of Medical Science, Center for Allergy, Center for Medical Education, Nihon University School of Medicine, Tokyo, 173-8610, Japan., Kunisawa J; International Research and Development Center for Mucosal Vaccines, The Institute of Medical Science, The University of Tokyo, Tokyo, 108-8639, Japan.; Laboratory of Vaccine Materials, Center for Vaccine and Adjuvant Research and Laboratory of Gut Environmental System, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka, 567-0085, Japan., Kubo M; Laboratory for Cytokine Regulation, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, 230-0045, Japan.; Division of Molecular Pathology, Research Institute for Biomedical Science, Tokyo University of Science, Chiba, 278-0022, Japan., Takemura N; Department of Innovative Medicine and Mucosal Immunology, Graduate School of Medicine, Chiba University, Chiba, 260-8670, Japan.; International Research and Development Center for Mucosal Vaccines, The Institute of Medical Science, The University of Tokyo, Tokyo, 108-8639, Japan.; Laboratory of Bioresponse Regulation, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka, 565-0871, Japan., Uematsu S; Department of Innovative Medicine and Mucosal Immunology, Graduate School of Medicine, Chiba University, Chiba, 260-8670, Japan.; International Research and Development Center for Mucosal Vaccines, The Institute of Medical Science, The University of Tokyo, Tokyo, 108-8639, Japan.; Department of Immunology and Genomics, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan., Akira S; Laboratory of Host Defense, WPI Immunology Frontier Research Center, Osaka University, Osaka, 565-0871, Japan.; Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Osaka, 565-0871, Japan., Kitaura J; Atopy Research Center, Juntendo University Graduate School of Medicine, Tokyo, 113-8421, Japan., Takahashi T; Department of Pediatrics, Keio University School of Medicine, Tokyo, 160-8582, Japan., Nakayama T; Department of Immunology, Graduate School of Medicine, Chiba University, Chiba, 260-8670, Japan., Kiyono H; Department of Mucosal Immunology, The University of Tokyo Distinguished Professor Unit, The Institute of Medical Science, The University of Tokyo, Tokyo, 108-8639, Japan. kiyono@ims.u-tokyo.ac.jp.; Department of Pediatrics, Keio University School of Medicine, Tokyo, 160-8582, Japan. kiyono@ims.u-tokyo.ac.jp.; Division of Gastroenterology, Department of Medicine, CU-UCSD Center for Mucosal Immunology, Allergy and Vaccines (CU-UCSD cMAV), University of California, San Diego, CA, 92093-0956, USA. kiyono@ims.u-tokyo.ac.jp.; Institute for Global Prominent Research, Chiba University, Chiba, 260-8670, Japan. kiyono@ims.u-tokyo.ac.jp.; Department of Immunology, Graduate School of Medicine, Chiba University, Chiba, 260-8670, Japan. kiyono@ims.u-tokyo.ac.jp.
Jazyk: angličtina
Zdroj: Mucosal immunology [Mucosal Immunol] 2021 May; Vol. 14 (3), pp. 640-651. Date of Electronic Publication: 2020 Dec 10.
DOI: 10.1038/s41385-020-00358-3
Abstrakt: Oral immunotherapy (OIT) is an effective approach to controlling food allergy. Although the detailed molecular and cellular mechanisms of OIT are unknown currently, they must be understood to advance the treatment of allergic diseases in general. To elucidate the mechanisms of OIT, especially during the immunological transition from desensitization to allergy regulation, we generated a clinical OIT murine model and used it to examine immunological events of OIT. We found that in mice that completed OIT successfully, desensitized mast cells (MCs) showed functionally beneficial alterations, such as increased induction of regulatory cytokines and enhanced expansion of regulatory T cells. Importantly, these regulatory-T-cell-mediated inhibitions of allergic responses were dramatically decreased in mice lacking OIT-induced desensitized MC. Collectively, these findings show that the desensitization process modulates the activation of MCs, leading directly to enhanced induction of regulatory-T-cell expansion and promotion of clinical allergic unresponsiveness. Our results suggest that efficiently inducing regulatory MCs is a novel strategy for the treatment of allergic disease.
Databáze: MEDLINE
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