title: Inhaled Fine Particles Induce Alveolar Macrophage Death and Interleukin-1α Release to Promote Inducible Bronchus-Associated Lymphoid Tissue Formation.
abstract: Particulate pollution is thought to function as an adjuvant that can induce allergic responses. However, the exact cell types and immunological factors that initiate the lung-specific immune responses are unclear. We found that upon intratracheal instillation, particulates such as aluminum salts and silica killed alveolar macrophages (AMs), which then released interleukin-1α (IL-1α) and caused inducible bronchus-associated lymphoid tissue (iBALT) formation in the lung. IL-1α release continued for up to 2 weeks after particulate exposure, and type-2 allergic immune responses were induced by the inhalation of antigen during IL-1α release and iBALT formation, even long after particulate instillation. Recombinant IL-1α was sufficient to induce iBALTs, which coincided with subsequent immunoglobulin E responses, and IL-1-receptor-deficient mice failed to induce iBALT formation. Therefore, the AM-IL-1α-iBALT axis might be a therapeutic target for particulate-induced allergic inflammation.
authors.affiliation: Laboratory of Vaccine Science, WPI Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan; Laboratory of Vaccine Design, Center for Drug Design Research, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka 567-0085, Japan; Laboratory of Adjuvant Innovation, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka 567-0085, Japan. Electronic address: kuroetu@ifrec.osaka-u.ac.jp.
authors.forename: Etsushi
authors.initials: E
authors.lastname: Kuroda
authors.affiliation: Laboratory of Adjuvant Innovation, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka 567-0085, Japan; Department of Pediatrics, Yokohama City University Graduate School of Medicine, Kanagawa 236-0004, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Ozasa
authors.affiliation: Laboratory of Vaccine Science, WPI Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan.
authors.forename: Burcu
authors.initials: B
authors.lastname: Temizoz
authors.affiliation: Laboratory of Vaccine Science, WPI Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Ohata
authors.affiliation: Laboratory of Adjuvant Innovation, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka 567-0085, Japan; Immunology Programme and Department of Microbiology, Centre for Life Science, National University of Singapore 117456, Singapore; NUS Graduate School of Integrated Sciences & Engineering, National University of Singapore 117456, Singapore.
authors.forename: Christine X
authors.initials: CX
authors.lastname: Koo
authors.affiliation: Laboratory of Vaccine Science, WPI Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan; Laboratory of Adjuvant Innovation, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka 567-0085, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Kanuma
authors.affiliation: Laboratory of Vaccine Science, WPI Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan; Laboratory of Adjuvant Innovation, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka 567-0085, Japan.
authors.forename: Takato
authors.initials: T
authors.lastname: Kusakabe
authors.affiliation: Laboratory of Adjuvant Innovation, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka 567-0085, Japan; Department of Pediatrics, Yokohama City University Graduate School of Medicine, Kanagawa 236-0004, Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Kobari
authors.affiliation: Health Research Institute, National Institute of Advanced Industrial Science and Technology, Kagawa 761-0395, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Horie
authors.affiliation: Department of Occupational Pneumology, University of Occupational and Environmental Health, Japan, Fukuoka 807-8555, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Morimoto
authors.affiliation: Department of Dermatology, Kyoto University, Graduate School of Medicine, Kyoto 606-8317, Japan.
authors.forename: Saeko
authors.initials: S
authors.lastname: Nakajima
authors.affiliation: Department of Dermatology, Kyoto University, Graduate School of Medicine, Kyoto 606-8317, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Kabashima
authors.affiliation: Immunology Program, Benaroya Research Institute, Seattle, WA 98101-2795, USA.
authors.forename: Steven F
authors.initials: SF
authors.lastname: Ziegler
authors.affiliation: Research Institute for Biomedical Science, Tokyo University of Science, Chiba 278-0222, Japan.
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Iwakura
authors.affiliation: Laboratory of Lymphocyte Differentiation, WPI Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Ise
authors.affiliation: Laboratory of Lymphocyte Differentiation, WPI Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Kurosaki
authors.affiliation: Vaccine Materials, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka 567-0085, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Nagatake
authors.affiliation: Vaccine Materials, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka 567-0085, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Kunisawa
authors.affiliation: Department of Mucosal Immunology, School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan; Division of Innate Immune Regulation, International Research and Development Center for Mucosal Vaccines, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Takemura
authors.affiliation: Department of Mucosal Immunology, School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan; Division of Innate Immune Regulation, International Research and Development Center for Mucosal Vaccines, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Uematsu
authors.affiliation: Laboratory of Vaccine Science, WPI Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan; Laboratory of Adjuvant Innovation, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka 567-0085, Japan; Vaccine Research Development Office, Advanced Drug Research Laboratories, Sohyaku. Innovative Research Division, Mitsubishi Tanabe Pharma Corporation, Kanagawa 227-0033, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Hayashi
authors.affiliation: Laboratory of Adjuvant Innovation, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka 567-0085, Japan; Vaccine Dynamics Project, BIKEN Innovative Vaccine Research Alliance Laboratories, Research Institute for Microbial Diseases, Osaka, 565-0871, Japan.
authors.forename: Taiki
authors.initials: T
authors.lastname: Aoshi
authors.affiliation: Laboratory of Vaccine Science, WPI Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan; Laboratory of Adjuvant Innovation, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka 567-0085, Japan; La Jolla Institute for Allergy and Immunology, La Jolla, CA, 92037, USA.
authors.forename: Kouji
authors.initials: K
authors.lastname: Kobiyama
authors.affiliation: Laboratory of Malaria Immunology, WPI Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan.
authors.forename: Cevayir
authors.initials: C
authors.lastname: Coban
authors.affiliation: Laboratory of Vaccine Science, WPI Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan; Laboratory of Vaccine Design, Center for Drug Design Research, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka 567-0085, Japan; Laboratory of Adjuvant Innovation, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka 567-0085, Japan. Electronic address: kenishii@biken.osaka-u.ac.jp.
authors.forename: Ken J
authors.initials: KJ
authors.lastname: Ishii
mesh_terms: D017607:Aluminum Compounds / Q000633:toxicity; D000818:Animals; D001980:Bronchi / Q000276:immunology*; D005260:Female; D053582:Interleukin-1alpha / Q000276:immunology*; D008221:Lymphoid Tissue / Q000276:immunology*; D016676:Macrophages, Alveolar / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D052638:Particulate Matter / Q000633:toxicity*; D012822:Silicon Dioxide / Q000633:toxicity
chemical_list: D017607:Aluminum Compounds; D053582:Interleukin-1alpha; D052638:Particulate Matter; D012822:Silicon Dioxide
keywords: IL-1α; IgE; Particulate; alveolar macrophages; iBALT