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

Autor: Decque A; Nuclear Organization and Oncogenesis Unit, Institut Pasteur, Paris, France.; INSERM, U993, Paris, France., Joffre O; 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., Magalhaes JG; Centre de Recherche, Institut Curie, Paris, France.; INSERM, U932, Paris, France., Cossec JC; Nuclear Organization and Oncogenesis Unit, Institut Pasteur, Paris, France.; INSERM, U993, Paris, France., Blecher-Gonen R; Department of Immunology, Weizmann Institute, Rehovot, Israel., Lapaquette P; Nuclear Organization and Oncogenesis Unit, Institut Pasteur, Paris, France.; INSERM, U993, Paris, France., Silvin A; Centre de Recherche, Institut Curie, Paris, France.; INSERM, U932, Paris, France., Manel N; Centre de Recherche, Institut Curie, Paris, France.; INSERM, U932, Paris, France., Joubert PE; Laboratory of Dendritic Cell Immunobiology, Institut Pasteur, INSERM U818, Paris, France., Seeler JS; Nuclear Organization and Oncogenesis Unit, Institut Pasteur, Paris, France.; INSERM, U993, Paris, France., Albert ML; Laboratory of Dendritic Cell Immunobiology, Institut Pasteur, INSERM U818, Paris, France., Amit I; Department of Immunology, Weizmann Institute, Rehovot, Israel., Amigorena S; Centre de Recherche, Institut Curie, Paris, France.; INSERM, U932, Paris, France., Dejean A; Nuclear Organization and Oncogenesis Unit, Institut Pasteur, Paris, France.; INSERM, U993, Paris, France.
Jazyk: angličtina
Zdroj: Nature immunology [Nat Immunol] 2016 Feb; Vol. 17 (2), pp. 140-9. Date of Electronic Publication: 2015 Dec 14.
DOI: 10.1038/ni.3342
Abstrakt: 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.
Databáze: MEDLINE
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