title: T(H)17 cells promote microbial killing and innate immune sensing of DNA via interleukin 26.
abstract: Interleukin 17-producing helper T cells (T(H)17 cells) have a major role in protection against infections and in mediating autoimmune diseases, yet the mechanisms involved are incompletely understood. We found that interleukin 26 (IL-26), a human T(H)17 cell-derived cytokine, is a cationic amphipathic protein that kills extracellular bacteria via membrane-pore formation. Furthermore, T(H)17 cell-derived IL-26 formed complexes with bacterial DNA and self-DNA released by dying bacteria and host cells. The resulting IL-26-DNA complexes triggered the production of type I interferon by plasmacytoid dendritic cells via activation of Toll-like receptor 9, but independently of the IL-26 receptor. These findings provide insights into the potent antimicrobial and proinflammatory function of T(H)17 cells by showing that IL-26 is a natural human antimicrobial that promotes immune sensing of bacterial and host cell death.
authors.affiliation: 1] Department of Immunology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA. [2] Department of Dermatology, Heinrich-Heine-University Medical Faculty, Düsseldorf, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Meller
authors.affiliation: Department of Dermatology, University Hospital CHUV, Lausanne, Switzerland.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Di Domizio
authors.affiliation: Department of Immunology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Kui S
authors.initials: KS
authors.lastname: Voo
authors.affiliation: Department of Dermatology, Heinrich-Heine-University Medical Faculty, Düsseldorf, Germany.
authors.forename: Heike C
authors.initials: HC
authors.lastname: Friedrich
authors.affiliation: 1] Department of Immunology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA. [2] Department of Infectious Diseases, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Georgios
authors.initials: G
authors.lastname: Chamilos
authors.affiliation: Department of Immunology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Dipyaman
authors.initials: D
authors.lastname: Ganguly
authors.affiliation: Department of Dermatology, University Hospital CHUV, Lausanne, Switzerland.
authors.forename: Curdin
authors.initials: C
authors.lastname: Conrad
authors.affiliation: Department of Immunology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Josh
authors.initials: J
authors.lastname: Gregorio
authors.affiliation: Department of Infectious Diseases, University Hospital CHUV, Lausanne, Switzerland.
authors.forename: Didier
authors.initials: D
authors.lastname: Le Roy
authors.affiliation: Department of Infectious Diseases, University Hospital CHUV, Lausanne, Switzerland.
authors.forename: Thierry
authors.identifier: 0000000293580109
authors.initials: T
authors.lastname: Roger
authors.affiliation: School of Molecular and Cell Biology, University of Leeds, Leeds, UK.
authors.forename: John E
authors.initials: JE
authors.lastname: Ladbury
authors.affiliation: Department of Dermatology, Heinrich-Heine-University Medical Faculty, Düsseldorf, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Homey
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, Texas, USA.
authors.forename: Stanley
authors.initials: S
authors.lastname: Watowich
authors.affiliation: Division of Dermatology, UCLA David Geffen School of Medicine, Los Angeles, California, USA.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Modlin
authors.affiliation: Department of Infectious Diseases, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Dimitrios P
authors.initials: DP
authors.lastname: Kontoyiannis
authors.affiliation: Department of Respiratory, Inflammation and Autoimmunity, MedImmune, Gaithersburg, Maryland, USA.
authors.forename: Yong-Jun
authors.initials: YJ
authors.lastname: Liu
authors.affiliation: Division of Biological and Environmental Sciences &Engineering, King Abdullah University of Science and Technology (KAUST), Thuwal, Kingdom of Saudi Arabia.
authors.forename: Stefan T
authors.initials: ST
authors.lastname: Arold
authors.affiliation: 1] Department of Immunology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA. [2] Department of Dermatology, University Hospital CHUV, Lausanne, Switzerland.
authors.forename: Michel
authors.initials: M
authors.lastname: Gilliet
mesh_terms: D000818:Animals; D004247:DNA / Q000276:immunology*; D004269:DNA, Bacterial / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D007370:Interferon Type I / Q000276:immunology / Q000378:metabolism; D007378:Interleukins / Q000276:immunology*; D051379:Mice; D011565:Psoriasis / Q000276:immunology; D018123:Receptors, Interleukin / Q000276:immunology / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology*; D051217:Toll-Like Receptor 9 / Q000276:immunology*
chemical_list: D004269:DNA, Bacterial; C406767:IL26 protein, human; D007370:Interferon Type I; D007378:Interleukins; D018123:Receptors, Interleukin; D051217:Toll-Like Receptor 9; D004247:DNA