title: The RNA Binding Protein Mex-3B Is Required for IL-33 Induction in the Development of Allergic Airway Inflammation.
abstract: Allergic airway inflammation is one of the primary features of allergic asthma. Interleukin-33 (IL-33) is recognized as a key pro-inflammatory cytokine that mediates allergic airway inflammation, and its expression is elevated in this condition, but little is known about the regulatory mechanisms underlying IL-33 induction. Here, we show that the RNA binding protein Mex-3B plays a critical role in the induction of IL-33 in the development of allergic airway inflammation. We generated Mex3b(-/-) mice and found that they develop significantly less airway inflammation than wild-type mice due to reduced induction of IL-33. Furthermore, we show that Mex-3B directly upregulates IL-33 expression by inhibiting miR-487b-3p-mediated repression of IL-33. Moreover, we show that inhalation of an antisense oligonucleotide targeting Mex-3B suppresses allergic airway inflammation. Our data identify a signaling pathway that post-transcriptionally regulates IL-33 expression and suggest that Mex-3B could be a promising molecular target for the treatment of allergic asthma.
authors.affiliation: Laboratory of Molecular and Genetic Information, Institute for Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Yamazumi
authors.affiliation: Department of Allergy and Rheumatology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
authors.forename: Oh
authors.initials: O
authors.lastname: Sasaki
authors.affiliation: Department of Allergy and Rheumatology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Imamura
authors.affiliation: Laboratory of Molecular and Genetic Information, Institute for Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
authors.forename: Takeaki
authors.initials: T
authors.lastname: Oda
authors.affiliation: Laboratory of Molecular and Genetic Information, Institute for Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Ohno
authors.affiliation: Laboratory of Molecular and Genetic Information, Institute for Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Shiozaki-Sato
authors.affiliation: Department of Molecular Immunology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8549, Japan.
authors.forename: Shigenori
authors.initials: S
authors.lastname: Nagai
authors.affiliation: Laboratory of Molecular and Genetic Information, Institute for Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
authors.forename: Saki
authors.initials: S
authors.lastname: Suyama
authors.affiliation: Laboratory of Molecular and Genetic Information, Institute for Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Kamoshida
authors.affiliation: Laboratory of Molecular and Genetic Information, Institute for Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Funato
authors.affiliation: Department of Molecular Immunology, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Teruhito
authors.initials: T
authors.lastname: Yasui
authors.affiliation: Department of Molecular Immunology, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Kikutani
authors.affiliation: Department of Allergy and Rheumatology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Yamamoto
authors.affiliation: Department of Allergy and Rheumatology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan; Institute of Respiratory Immunology, Shibuya Clinic for Respiratory Diseases and Allergology, Tokyo 150-0002, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Dohi
authors.affiliation: Laboratory for Immune Cell Systems, RIKEN Research Center for Integrative Medical Sciences (IMS), 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan.
authors.forename: Shigeo
authors.initials: S
authors.lastname: Koyasu
authors.affiliation: Laboratory of Molecular and Genetic Information, Institute for Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan. Electronic address: akiyama@iam.u-tokyo.ac.jp.
authors.forename: Tetsu
authors.initials: T
authors.lastname: Akiyama
mesh_terms: D000818:Animals; D001483:Base Sequence; D016535:Bronchial Hyperreactivity / Q000139:chemically induced / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D004847:Epithelial Cells / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D005786:Gene Expression Regulation; D006801:Humans; D000067596:Interleukin-33 / Q000235:genetics / Q000276:immunology*; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics / Q000276:immunology*; D009690:Nucleic Acid Conformation; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D010047:Ovalbumin; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D016601:RNA-Binding Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology; D020545:Respiratory Mucosa / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D015398:Signal Transduction; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology / Q000473:pathology
chemical_list: C506535:Il33 protein, mouse; D000067596:Interleukin-33; C000589341:MEX3B protein, mouse; C000609796:MIRN487 microRNA, mouse; D035683:MicroRNAs; D016376:Oligonucleotides, Antisense; D016601:RNA-Binding Proteins; D010047:Ovalbumin