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

First Author  Legutko A Year  2011
Journal  J Immunol Volume  187
Issue  9 Pages  4517-29
PubMed ID  21948987 Mgi Jnum  J:179447
Mgi Id  MGI:5302441 Doi  10.4049/jimmunol.1101493
Citation  Legutko A, et al. (2011) Sirtuin 1 promotes Th2 responses and airway allergy by repressing peroxisome proliferator-activated receptor-gamma activity in dendritic cells. J Immunol 187(9):4517-29
abstractText  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-kappaB. 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-gamma 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.
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