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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.

Original publication

DOI

10.4049/jimmunol.1101493

Type

Journal article

Journal

J Immunol

Publication Date

01/11/2011

Volume

187

Pages

4517 - 4529

Keywords

Animals, Asthma, Bronchial Hyperreactivity, Cell Differentiation, Cell Movement, Cells, Cultured, Dendritic Cells, Female, Immunophenotyping, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Knockout, Mice, Transgenic, PPAR gamma, Sirtuin 1, Th2 Cells