title: Type I interferon restricts type 2 immunopathology through the regulation of group 2 innate lymphoid cells.
abstract: Viral respiratory tract infections are the main causative agents of the onset of infection-induced asthma and asthma exacerbations that remain mechanistically unexplained. Here we found that deficiency in signaling via type I interferon receptor led to deregulated activation of group 2 innate lymphoid cells (ILC2 cells) and infection-associated type 2 immunopathology. Type I interferons directly and negatively regulated mouse and human ILC2 cells in a manner dependent on the transcriptional activator ISGF3 that led to altered cytokine production, cell proliferation and increased cell death. In addition, interferon-γ (IFN-γ) and interleukin 27 (IL-27) altered ILC2 function dependent on the transcription factor STAT1. These results demonstrate that type I and type II interferons, together with IL-27, regulate ILC2 cells to restrict type 2 immunopathology.
authors.affiliation: Department of Microbiology and Immunology, Complex Traits Group, McGill University, Montréal, Canada.
authors.forename: Claudia U
authors.initials: CU
authors.lastname: Duerr
authors.affiliation: Department of Physiology, Complex Traits Group, McGill University, Montréal, Canada.
authors.forename: Connor D A
authors.initials: CD
authors.lastname: McCarthy
authors.affiliation: Department of Microbiology and Immunology, Complex Traits Group, McGill University, Montréal, Canada.
authors.forename: Barbara C
authors.initials: BC
authors.lastname: Mindt
authors.affiliation: Immunoregulation Laboratories, The Research Center of the Centre Hospitalier de L'Université de Montréal, Montréal, Québec, Canada.
authors.forename: Manuel
authors.initials: M
authors.lastname: Rubio
authors.affiliation: Department of Microbiology and Immunology, Microbiome and Disease Tolerance Center, McGill University, Lyman Duff Medical Building, Montréal, Canada.
authors.forename: Alexandre P
authors.initials: AP
authors.lastname: Meli
authors.affiliation: Diaccurate, Institut Pasteur, Paris, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Pothlichet
authors.affiliation: Department of Human Genetics, Complex Traits Group, McGill University, Montréal, Canada.
authors.forename: Megan M
authors.initials: MM
authors.lastname: Eva
authors.affiliation: Department of Pharmacology, Université de Montréal, Montréal, Canada.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Gauchat
authors.affiliation: Meakins Christie Laboratories, McGill University and Department of Critical Care, The Research Institute of the McGill University Health Center, Montréal, Canada.
authors.forename: Salman T
authors.initials: ST
authors.lastname: Qureshi
authors.affiliation: Department of Pediatrics, McGill University, Meakins Christie Laboratories, The Research Institute of the McGill University Health Center, Montréal, Canada.
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Mazer
authors.affiliation: Department of Pathology and Molecular Medicine, McMaster Immunology Research Center, Institute for Infectious Disease Research, McMaster University, Hamilton, Canada.
authors.forename: Karen L
authors.initials: KL
authors.lastname: Mossman
authors.affiliation: Department of Human Genetics, Complex Traits Group, McGill University, Montréal, Canada.|Department of Medicine, Complex Traits Group, McGill University, Montréal, Canada.
authors.forename: Danielle
authors.initials: D
authors.lastname: Malo
authors.affiliation: Department of Medical Genetics and Molecular Biochemistry, Temple University School of Medicine, Philadelphia, Pennsylvania, USA.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Gamero
authors.affiliation: Department of Human Genetics, Complex Traits Group, McGill University, Montréal, Canada.|Department of Medicine, Complex Traits Group, McGill University, Montréal, Canada.
authors.forename: Silvia M
authors.initials: SM
authors.lastname: Vidal
authors.affiliation: Department of Microbiology and Immunology, Microbiome and Disease Tolerance Center, McGill University, Lyman Duff Medical Building, Montréal, Canada.
authors.forename: Irah L
authors.initials: IL
authors.lastname: King
authors.affiliation: Immunoregulation Laboratories, The Research Center of the Centre Hospitalier de L'Université de Montréal, Montréal, Québec, Canada.|Department of Medicine, Université de Montréal, Montréal, Canada.
authors.forename: Marika
authors.initials: M
authors.lastname: Sarfati
authors.affiliation: Department of Microbiology and Immunology, Complex Traits Group, McGill University, Montréal, Canada.|Department of Physiology, Complex Traits Group, McGill University, Montréal, Canada.
authors.forename: Jörg H
authors.initials: JH
authors.lastname: Fritz
mesh_terms: D000818:Animals; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D007370:Interferon Type I / Q000276:immunology*; D008214:Lymphocytes / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009976:Orthomyxoviridae Infections / Q000276:immunology; D060888:Real-Time Polymerase Chain Reaction; D012141:Respiratory Tract Infections / Q000276:immunology* / Q000473:pathology
chemical_list: D016207:Cytokines; D007370:Interferon Type I