title: Innate-like function of memory Th17 cells for enhancing endotoxin-induced acute lung inflammation through IL-22.
abstract: Lipopolysaccharide (LPS)-induced acute lung injury (ALI) is known as a mouse model of acute respiratory distress syndrome; however, the function of T-cell-derived cytokines in ALI has not yet been established. We found that LPS challenge in one lung resulted in a rapid induction of innate-type pro-inflammatory cytokines such as IL-6 and TNF-α, followed by the expression of T-cell-type cytokines, including IL-17, IL-22 and IFN-γ. We discovered that IL-23 is important for ALI, since blockage of IL-23 by gene disruption or anti-IL-12/23p40 antibody treatment reduced neutrophil infiltration and inflammatory cytokine secretion into the bronchoalveolar lavage fluid (BALF). IL-23 was mostly produced from F4/80(+)CD11c(+) alveolar macrophages, and IL-23 expression was markedly reduced by the pre-treatment of mice with antibiotics, suggesting that the development of IL-23-producing macrophages required commensal bacteria. Unexpectedly, among T-cell-derived cytokines, IL-22 rather than IL-17 or IFN-γ played a major role in LPS-induced ALI. IL-22 protein levels were higher than IL-17 in the BALF after LPS instillation, and the major source of IL-22 was memory Th17 cells. Lung memory CD4(+) T cells had a potential to produce IL-22 at higher levels than IL-17 in response to IL-1β plus IL-23 without TCR stimulation. Our study revealed an innate-like function of the lung memory Th17 cells that produce IL-22 in response to IL-23 and are involved in exaggeration of ALI.
authors.affiliation: Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo 160-8582, Japan Department of Anesthesiology, Keio University School of Medicine, Tokyo 160-8582, Japan.
authors.forename: Ryota
authors.initials: R
authors.lastname: Sakaguchi
authors.affiliation: Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo 160-8582, Japan.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Chikuma
authors.affiliation: Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo 160-8582, Japan PRESTO (Precursory Research for Embryonic Science and Technology), Chiyoda-ku, Tokyo 102-0075, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Shichita
authors.affiliation: Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo 160-8582, Japan.
authors.forename: Rimpei
authors.initials: R
authors.lastname: Morita
authors.affiliation: Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo 160-8582, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Sekiya
authors.affiliation: Department of Immunology, Genentech, 1 DNA Way, San Francisco, CA 94080, USA.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Ouyang
authors.affiliation: Department of Anesthesiology, Keio University School of Medicine, Tokyo 160-8582, Japan.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Ueda
authors.affiliation: Department of Anesthesiology, Keio University School of Medicine, Tokyo 160-8582, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Seki
authors.affiliation: Department of Anesthesiology, Keio University School of Medicine, Tokyo 160-8582, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Morisaki
authors.affiliation: Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo 160-8582, Japan yoshimura@a6.keio.jp.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Yoshimura
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D000818:Animals; D018893:Bronchoalveolar Lavage; D016207:Cytokines / Q000235:genetics / Q000276:immunology*; D007113:Immunity, Innate / Q000187:drug effects* / Q000235:genetics; D007249:Inflammation / Q000139:chemically induced / Q000235:genetics / Q000276:immunology / Q000473:pathology; D008070:Lipopolysaccharides / Q000633:toxicity*; D008168:Lung / Q000276:immunology* / Q000473:pathology; D008264:Macrophages / Q000276:immunology / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D058504:Th17 Cells / Q000276:immunology* / Q000473:pathology
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides
keywords: acute lung injury; antibiotics; commensal bacteria; memory Th17