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Sirtuin 1 promotes Th2 responses and airway allergy by repressing peroxisome proliferator-activated receptor-γ activity in dendritic cells

par Legutko, Agnieszka;Marichal, Thomas;Fiévez, Laurence;Bedoret, Denis;Mayer, Alice ;De Vries, Hilda;Klotz, Luisa;Drion, Pierre-Vincent;Heirman, Carlo;Cataldo, Didier;Louis, Renaud;Thielemans, Kris M.;Andris, Fabienne ;Leo, Oberdan ;Lekeux, Pierre;Desmet, Christophe;Bureau, Fabrice
Référence The Journal of immunology, 187, 9, page (4517-4529)
Publication Publié, 2011-11

Article révisé par les pairs

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Résumé :

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. Copyright©2011 by The American Association of Immunologists, Inc.