Type I interferon restricts type 2 immunopathology through the regulation of group 2 innate lymphoid cells

Dysregulation of group 2 innate lymphoid cells has been linked to virus-induced asthma. Fritz and colleagues demonstrate that deficiency in signaling via type I interferons in these cells can lead to dysregulated type 2 immunity during respiratory viral infection. Viral respiratory tract infections...

Full description

Saved in:
Bibliographic Details
Published inNature immunology Vol. 17; no. 1; pp. 65 - 75
Main Authors Duerr, Claudia U, McCarthy, Connor D A, Mindt, Barbara C, Rubio, Manuel, Meli, Alexandre P, Pothlichet, Julien, Eva, Megan M, Gauchat, Jean-François, Qureshi, Salman T, Mazer, Bruce D, Mossman, Karen L, Malo, Danielle, Gamero, Ana M, Vidal, Silvia M, King, Irah L, Sarfati, Marika, Fritz, Jörg H
Format Journal Article
LanguageEnglish
Published New York Nature Publishing Group US 01.01.2016
Nature Publishing Group
Subjects
13/21
13/31
13/51
13/95
631/250
631/250/2504/2506
64/60
Animals
Asthma
Biomedicine
Cell receptors
Cellular signal transduction
Cytokines - biosynthesis
Cytokines - immunology
Disease Models, Animal
Enzyme-Linked Immunosorbent Assay
Flow Cytometry
Genetic aspects
Health aspects
Humans
Immune response
Immunity, Innate - immunology
Immunology
Infectious Diseases
Interferon Type I - immunology
Lymphocytes - immunology
Mice
Mice, Inbred C57BL
Mice, Knockout
Orthomyxoviridae Infections - immunology
Properties
Real-Time Polymerase Chain Reaction
Respiratory tract
Respiratory Tract Infections - immunology
Respiratory Tract Infections - pathology
Online AccessGet full text

Cover

More Information
Summary:Dysregulation of group 2 innate lymphoid cells has been linked to virus-induced asthma. Fritz and colleagues demonstrate that deficiency in signaling via type I interferons in these cells can lead to dysregulated type 2 immunity during respiratory viral infection. 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.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
AUTHOR CONTRIBUTIONS
C.U.D. and J.H.F. designed the conceptual framework of the study, designed experiments and wrote the paper; C.U.D., C.D.A.M. and B.C.M. designed and performed experiments and analyzed data; M.R. and M.S. performed experiments with human ILC2 cells and helped to design and interpret experiments; A.P.M. and I.L.K. provided H. polygyrus, performed infections and helped to design and interpret experiments; J.P. and S.M.V. provided influenza virus and helped to design and interpret experiments; M.M.E. and D.M. provided STAT4-mutant mice; J.-F.G. provided reagents and expertise for experiments with IL-27; S.T.Q. provided STAT1-deficient BM; B.D.M. provided equipment and expertise for AHR measurements; K.L.M. provided IRF9-deficient BM; A.M.G. provided STAT1- and STAT2-deficient BM; and all authors provided input throughout the study and the writing of the manuscript.
ISSN:1529-2908
1529-2916
DOI:10.1038/ni.3308