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Article Dans Une Revue Nature Immunology Année : 2016

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

Résumé

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

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Immunologie
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Dates et versions

pasteur-01380657 , version 1 (13-10-2016)

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Adrien Decque, Olivier Joffre, Joao G Magalhaes, Jack-Christophe Cossec, Ronnie Blecher-Gonen, et al.. Sumoylation coordinates the repression of inflammatory and anti-viral gene-expression programs during innate sensing. Nature Immunology, 2016, 17 (2), pp.140 - 149. ⟨10.1038/ni.3342⟩. ⟨pasteur-01380657⟩
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