Sumoylation coordinates the repression of inflammatory and anti-viral gene-expression programs during innate sensing

Sumolyation regulates wide-ranging biological processes, but its influence on innate immunity is unclear. Amigorena and colleagues show that sumoylation negatively regulates interferon-β expression and anti-viral immunity. Innate sensing of pathogens initiates inflammatory cytokine responses that ne...

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Bibliographic Details
Published in:	Nature immunology Vol. 17; no. 2; pp. 140 - 149
Main Authors:	Decque, Adrien, Joffre, Olivier, Magalhaes, Joao G, Cossec, Jack-Christophe, Blecher-Gonen, Ronnie, Lapaquette, Pierre, Silvin, Aymeric, Manel, Nicolas, Joubert, Pierre-Emmanuel, Seeler, Jacob-Sebastian, Albert, Matthew L, Amit, Ido, Amigorena, Sebastian, Dejean, Anne
Format:	Journal Article
Language:	English
Published:	New York Nature Publishing Group US 01-02-2016 Nature Publishing Group
Subjects:	13/31 13/95 38/61 631/250/2502 631/250/256 631/250/262/2106 64/110 82/80 Analysis Animals Antiviral agents Biological response modifiers Biomedicine Chromatin - genetics Chromatin - metabolism Cytokines Cytokines - metabolism Dendritic Cells - immunology Dendritic Cells - metabolism Disease Models, Animal Disease Resistance Disease Susceptibility Endotoxin shock Endotoxins Enhancer Elements, Genetic Gene expression Gene Expression Profiling Gene Expression Regulation Genetic Loci Health aspects Immunity, Innate Immunology Immunomodulation Infectious Diseases Inflammation Inflammation - genetics Inflammation - immunology Inflammation - metabolism Inflammation - virology Inflammation Mediators - metabolism Influence Innate immunity Interferon Interferon-beta - metabolism Life Sciences Lipopolysaccharides - immunology Mice Mice, Knockout Myeloid cells NF-κB protein Protein Binding Receptor, Interferon alpha-beta - metabolism Regulatory Elements, Transcriptional Risk factors Shock, Septic - genetics Shock, Septic - immunology Shock, Septic - metabolism Signal Transduction SUMO protein SUMO-1 Protein - metabolism Sumoylation - genetics Sumoylation - immunology Toll-like receptors Toll-Like Receptors - metabolism Ubiquitin β-Interferon France Gene regulation in immune cells Inflammation Pattern recognition receptors
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Summary:	Sumolyation regulates wide-ranging biological processes, but its influence on innate immunity is unclear. Amigorena and colleagues show that sumoylation negatively regulates interferon-β expression and anti-viral immunity. Innate sensing of pathogens initiates inflammatory cytokine responses that need to be tightly controlled. We found here that after engagement of Toll-like receptors (TLRs) in myeloid cells, deficient sumoylation caused increased secretion of transcription factor NF-κB–dependent inflammatory cytokines and a massive type I interferon signature. In mice, diminished sumoylation conferred susceptibility to endotoxin shock and resistance to viral infection. Overproduction of several NF-κB-dependent inflammatory cytokines required expression of the type I interferon receptor, which identified type I interferon as a central sumoylation-controlled hub for inflammation. Mechanistically, the small ubiquitin-like modifier SUMO operated from a distal enhancer of the gene encoding interferon-β ( Ifnb1 ) to silence both basal and stimulus-induced activity of the Ifnb1 promoter. Therefore, sumoylation restrained inflammation by silencing Ifnb1 expression and by strictly suppressing an unanticipated priming by type I interferons of the TLR-induced production of inflammatory cytokines.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1529-2908 1529-2916
DOI:	10.1038/ni.3342