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© Jacob SEELER & Anne DEJEAN, Institut Pasteur
Immunostaining of PML nuclear bodies involved in acute promyelocytic leukemia
Publication : Nature immunology

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

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Nature immunology - 14 Dec 2015

Decque A, Joffre O, Magalhaes JG, Cossec JC, Blecher-Gonen R, Lapaquette P, Silvin A, Manel N, Joubert PE, Seeler JS, Albert ML, Amit I, Amigorena S, Dejean A

Link to Pubmed [PMID] – 26657003

Nat. Immunol. 2016 Feb;17(2):140-9

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.

http://www.ncbi.nlm.nih.gov/pubmed/26657003