title: Sirtuin 1 promotes Th2 responses and airway allergy by repressing peroxisome proliferator-activated receptor-γ activity in dendritic cells.
abstract: Sirtuins are a unique class of NAD(+)-dependent deacetylases that regulate diverse biological functions such as aging, metabolism, and stress resistance. Recently, it has been shown that sirtuins may have anti-inflammatory activities by inhibiting proinflammatory transcription factors such as NF-κB. In contrast, we report in this study that pharmacological inhibition of sirtuins dampens adaptive Th2 responses and subsequent allergic inflammation by interfering with lung dendritic cell (DC) function in a mouse model of airway allergy. Using genetic engineering, we demonstrate that sirtuin 1 represses the activity of the nuclear receptor peroxisome proliferator-activated receptor-γ in DCs, thereby favoring their maturation toward a pro-Th2 phenotype. This study reveals a previously unappreciated function of sirtuin 1 in the regulation of DC function and Th2 responses, thus shedding new light on our current knowledge on the regulation of inflammatory processes by sirtuins.
authors.affiliation: Laboratory of Cellular and Molecular Physiology, Interdisciplinary Cluster for Applied Genoproteomics (GIGA-Research), University of Liège, Liège B-4000, Belgium.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Legutko
authors.forename: Thomas
authors.initials: T
authors.lastname: Marichal
authors.forename: Laurence
authors.initials: L
authors.lastname: Fiévez
authors.forename: Denis
authors.initials: D
authors.lastname: Bedoret
authors.forename: Alice
authors.initials: A
authors.lastname: Mayer
authors.forename: Hilda
authors.initials: H
authors.lastname: de Vries
authors.forename: Luisa
authors.initials: L
authors.lastname: Klotz
authors.forename: Pierre-Vincent
authors.initials: PV
authors.lastname: Drion
authors.forename: Carlo
authors.initials: C
authors.lastname: Heirman
authors.forename: Didier
authors.initials: D
authors.lastname: Cataldo
authors.forename: Renaud
authors.initials: R
authors.lastname: Louis
authors.forename: Kris
authors.initials: K
authors.lastname: Thielemans
authors.forename: Fabienne
authors.initials: F
authors.lastname: Andris
authors.forename: Oberdan
authors.initials: O
authors.lastname: Leo
authors.forename: Pierre
authors.initials: P
authors.lastname: Lekeux
authors.forename: Christophe J
authors.initials: CJ
authors.lastname: Desmet
authors.forename: Fabrice
authors.initials: F
authors.lastname: Bureau
mesh_terms: D000818:Animals; D001249:Asthma / Q000201:enzymology / Q000276:immunology* / Q000473:pathology; D016535:Bronchial Hyperreactivity / Q000235:genetics / Q000276:immunology / Q000473:pathology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D016130:Immunophenotyping; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D047495:PPAR gamma / Q000037:antagonists & inhibitors* / Q000378:metabolism; D056564:Sirtuin 1 / Q000037:antagonists & inhibitors / Q000502:physiology*; D018418:Th2 Cells / Q000201:enzymology / Q000276:immunology* / Q000473:pathology
chemical_list: D047495:PPAR gamma; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1