title: The interleukin-33-p38 kinase axis confers memory T helper 2 cell pathogenicity in the airway.
abstract: Memory CD4(+) T helper (Th) cells provide long-term protection against pathogens and are essential for the development of vaccines; however, some antigen-specific memory Th cells also drive immune-related pathology, including asthma. The mechanisms regulating the pathogenicity of memory Th cells remain poorly understood. We found that interleukin-33 (IL-33)-ST2 signals selectively licensed memory Th2 cells to induce allergic airway inflammation via production of IL-5 and that the p38 MAP kinase pathway was a central downstream target of IL-33-ST2 in memory Th2 cells. In addition, we found that IL-33 induced upregulation of IL-5 by memory CD4(+) T cells isolated from nasal polyps of patients with eosinophilic chronic rhinosinusitis. Thus, IL-33-ST2-p38 signaling appears to directly instruct pathogenic memory Th2 cells to produce IL-5 and induce eosinophilic inflammation.
authors.affiliation: Department of Immunology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana Chuo-ku, Chiba 260-8670, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Endo
authors.affiliation: Department of Advanced Allergology of the Airway, Graduate School of Medicine, Chiba University, 1-8-1 Inohana Chuo-ku, Chiba 260-8670, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Hirahara
authors.affiliation: Department of Otorhinolaryngology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana Chuo-ku, Chiba 260-8670, Japan.
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Iinuma
authors.affiliation: Department of Immunology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana Chuo-ku, Chiba 260-8670, Japan.
authors.forename: Kenta
authors.initials: K
authors.lastname: Shinoda
authors.affiliation: Department of Immunology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana Chuo-ku, Chiba 260-8670, Japan.
authors.forename: Damon J
authors.initials: DJ
authors.lastname: Tumes
authors.affiliation: Department of Immunology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana Chuo-ku, Chiba 260-8670, Japan.
authors.forename: Hikari K
authors.initials: HK
authors.lastname: Asou
authors.affiliation: Department of Immunology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana Chuo-ku, Chiba 260-8670, Japan.
authors.forename: Nao
authors.initials: N
authors.lastname: Matsugae
authors.affiliation: Department of Immunology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana Chuo-ku, Chiba 260-8670, Japan.
authors.forename: Kazushige
authors.initials: K
authors.lastname: Obata-Ninomiya
authors.affiliation: Department of Advanced Allergology of the Airway, Graduate School of Medicine, Chiba University, 1-8-1 Inohana Chuo-ku, Chiba 260-8670, Japan; Department of Otorhinolaryngology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana Chuo-ku, Chiba 260-8670, Japan.
authors.forename: Heizaburo
authors.initials: H
authors.lastname: Yamamoto
authors.affiliation: Department of Medical Immunology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana Chuo-ku, Chiba 260-8670, Japan.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Motohashi
authors.affiliation: Department of Allergy and Immunology, National Research Institute for Child Health and Development, 2-10-1 Okura Setagaya-ku, Tokyo 157-8535, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Oboki
authors.affiliation: Laboratory of Systems Biology, Center for Experimental Medicine and Systems Biology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Susumu
authors.initials: S
authors.lastname: Nakae
authors.affiliation: Department of Allergy and Immunology, National Research Institute for Child Health and Development, 2-10-1 Okura Setagaya-ku, Tokyo 157-8535, Japan.
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Saito
authors.affiliation: Department of Otorhinolaryngology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana Chuo-ku, Chiba 260-8670, Japan.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Okamoto
authors.affiliation: Department of Immunology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana Chuo-ku, Chiba 260-8670, Japan; CREST, Japan Science and Technology Agency, 1-8-1 Inohana Chuo-ku, Chiba 260-8670, Japan. Electronic address: tnakayama@faculty.chiba-u.jp.
authors.forename: Toshinori
authors.initials: T
authors.lastname: Nakayama
mesh_terms: D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000473:pathology; D002478:Cells, Cultured; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology; D007249:Inflammation / Q000276:immunology; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D015848:Interleukin-5 / Q000096:biosynthesis / Q000276:immunology*; D007378:Interleukins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009298:Nasal Polyps / Q000276:immunology; D011657:Pulmonary Eosinophilia / Q000276:immunology; D034622:RNA Interference; D034741:RNA, Small Interfering; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D018123:Receptors, Interleukin / Q000235:genetics / Q000276:immunology*; D012852:Sinusitis / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000276:immunology*
chemical_list: C486189:Il1rl1 protein, mouse; C506535:Il33 protein, mouse; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D015848:Interleukin-5; D007378:Interleukins; D034741:RNA, Small Interfering; D011948:Receptors, Antigen, T-Cell; D018123:Receptors, Interleukin; D048051:p38 Mitogen-Activated Protein Kinases