title: Sumoylation coordinates the repression of inflammatory and anti-viral gene-expression programs during innate sensing.
abstract: 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.
authors.affiliation: Nuclear Organization and Oncogenesis Unit, Institut Pasteur, Paris, France.|INSERM, U993, Paris, France.
authors.forename: Adrien
authors.initials: A
authors.lastname: Decque
authors.affiliation: Centre de Recherche, Institut Curie, Paris, France.|INSERM, U932, Paris, France.|INSERM U1043, Centre de Physiopathologie de Toulouse-Purpan, Université de Toulouse, Université Paul Sabatier, Toulouse, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Joffre
authors.affiliation: Centre de Recherche, Institut Curie, Paris, France.|INSERM, U932, Paris, France.
authors.forename: Joao G
authors.initials: JG
authors.lastname: Magalhaes
authors.affiliation: Nuclear Organization and Oncogenesis Unit, Institut Pasteur, Paris, France.|INSERM, U993, Paris, France.
authors.forename: Jack-Christophe
authors.initials: JC
authors.lastname: Cossec
authors.affiliation: Department of Immunology, Weizmann Institute, Rehovot, Israel.
authors.forename: Ronnie
authors.initials: R
authors.lastname: Blecher-Gonen
authors.affiliation: Nuclear Organization and Oncogenesis Unit, Institut Pasteur, Paris, France.|INSERM, U993, Paris, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Lapaquette
authors.affiliation: Centre de Recherche, Institut Curie, Paris, France.|INSERM, U932, Paris, France.
authors.forename: Aymeric
authors.initials: A
authors.lastname: Silvin
authors.affiliation: Centre de Recherche, Institut Curie, Paris, France.|INSERM, U932, Paris, France.
authors.forename: Nicolas
authors.identifier: http://orcid.org/0000-0002-1481-4430
authors.initials: N
authors.lastname: Manel
authors.affiliation: Laboratory of Dendritic Cell Immunobiology, Institut Pasteur, INSERM U818, Paris, France.
authors.forename: Pierre-Emmanuel
authors.initials: PE
authors.lastname: Joubert
authors.affiliation: Nuclear Organization and Oncogenesis Unit, Institut Pasteur, Paris, France.|INSERM, U993, Paris, France.
authors.forename: Jacob-Sebastian
authors.initials: JS
authors.lastname: Seeler
authors.affiliation: Laboratory of Dendritic Cell Immunobiology, Institut Pasteur, INSERM U818, Paris, France.
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Albert
authors.affiliation: Department of Immunology, Weizmann Institute, Rehovot, Israel.
authors.forename: Ido
authors.initials: I
authors.lastname: Amit
authors.affiliation: Centre de Recherche, Institut Curie, Paris, France.|INSERM, U932, Paris, France.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Amigorena
authors.affiliation: Nuclear Organization and Oncogenesis Unit, Institut Pasteur, Paris, France.|INSERM, U993, Paris, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Dejean
mesh_terms: D000818:Animals; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D060467:Disease Resistance; D004198:Disease Susceptibility; D004742:Enhancer Elements, Genetic; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D056426:Genetic Loci; D007113:Immunity, Innate; D056747:Immunomodulation; D007249:Inflammation / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism* / Q000821:virology; D018836:Inflammation Mediators / Q000378:metabolism; D016899:Interferon-beta / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D011485:Protein Binding; D053633:Receptor, Interferon alpha-beta / Q000378:metabolism; D050436:Regulatory Elements, Transcriptional; D025842:SUMO-1 Protein / Q000378:metabolism; D012772:Shock, Septic / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction; D058207:Sumoylation / Q000235:genetics / Q000276:immunology; D051193:Toll-Like Receptors / Q000378:metabolism
chemical_list: D002843:Chromatin; D016207:Cytokines; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D025842:SUMO-1 Protein; D051193:Toll-Like Receptors; D053633:Receptor, Interferon alpha-beta; D016899:Interferon-beta