The role of the sirtuin 6 in the innate immune response.

Abstract : In addition to its well-known role in energy metabolism, the nicotinamide adenine dinucleotide (NAD) has been recently shown to play an important role in the regulation of a vast array of cellular responses. The involvement of NAD in these regulatory processes is based on its ability to act as a substrate for a series of enzymes such as poly-ADP-ribosyl transferases and sirtuins, catalyzing respectively the ADP-ribosylation and/or deacetylation of cellular substrates. These enzymes have been shown to regulate gene expression at both transcriptional and post-transcriptional steps, suggesting that intracellular NAD levels can have profound effects on cell physiology well beyond cellular energetics. We and others have recently demonstrated that intracellular NAD levels can modulate the capacity of innate immune cells to produce pro-inflammatory mediators, suggesting a novel regulatory pathway linking cell metabolism to inflammation. More specifically, we demonstrated by pharmacological approaches and a positive screen the sirtuin 6 (SIRT6) as a NAD-dependent enzyme regulating TNF production in innate immune cells. By combining molecular biology and biochemical approaches, we wish to further explore the mechanisms by which SIRT6 controls the innate immune response. This study will possibly pave the way to the development of novel anti-inflammatory strategies of clinical relevance.
Promoteur/Supervisor : Prof. Kruys Véronique
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Centre de recherche/Research center : Laboratoire de Biologie moléculaire du g&eg
Faculté/Faculty : FacultĂ© des Sciences/Faculty of Sciences
Ecole doctorale/Graduate Colleges : Sciences/Science
Ecole doctorale thématique/Graduate School (French Only): Biologie Cellulaire et MolĂ©culaire, Biochimie (BCMB)

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