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dc.contributor.authorLasigliè, Deniseen_US
dc.contributor.authorBoero, Silviaen_US
dc.contributor.authorBauer, Ingaen_US
dc.contributor.authorMorando, Saraen_US
dc.contributor.authorDamonte, Patriziaen_US
dc.contributor.authorCea, Micheleen_US
dc.contributor.authorMonacelli, Fiammettaen_US
dc.contributor.authorOdetti, Paizioen_US
dc.contributor.authorBallestrero, Albertoen_US
dc.contributor.authorUccelli, Antonioen_US
dc.contributor.authorMostoslavsky, Raulen_US
dc.contributor.authorPoggi, Alessandroen_US
dc.contributor.authorNencioni, Alessioen_US
dc.date.accessioned2016-04-01T15:47:31Z
dc.date.issued2016en_US
dc.identifier.citationLasigliè, D., S. Boero, I. Bauer, S. Morando, P. Damonte, M. Cea, F. Monacelli, et al. 2016. “Sirt6 regulates dendritic cell differentiation, maturation, and function.” Aging (Albany NY) 8 (1): 34-47.en
dc.identifier.issn1945-4589en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:26318532
dc.description.abstractDendritic cells (DCs) are antigen-presenting cells that critically influence decisions about immune activation or tolerance. Impaired DC function is at the core of common chronic disorders and contributes to reduce immunocompetence during aging. Knowledge on the mechanisms regulating DC generation and function is necessary to understand the immune system and to prevent disease and immunosenescence. Here we show that the sirtuin Sirt6, which was previously linked to healthspan promotion, stimulates the development of myeloid, conventional DCs (cDCs). Sirt6-knockout (Sirt6KO) mice exhibit low frequencies of bone marrow cDC precursors and low yields of bone marrow-derived cDCs compared to wild-type (WT) animals. Sirt6KO cDCs express lower levels of class II MHC, of costimulatory molecules, and of the chemokine receptor CCR7, and are less immunostimulatory compared to WT cDCs. Similar effects in terms of differentiation and immunostimulatory capacity were observed in human monocyte-derived DCs in response to SIRT6 inhibition. Finally, while Sirt6KO cDCs show an overall reduction in their ability to produce IL-12, TNF-α and IL-6 secretion varies dependent on the stimulus, being reduced in response to CpG, but increased in response to other Toll-like receptor ligands. In conclusion, Sirt6 plays a crucial role in cDC differentiation and function and reduced Sirt6 activity may contribute to immunosenescence.en
dc.language.isoen_USen
dc.publisherImpact Journals LLCen
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4761712/pdf/en
dash.licenseLAAen_US
dc.subjectSirt6en
dc.subjectdendritic cellsen
dc.subjectTNF-αen
dc.subjectToll-like receptor ligandsen
dc.subjectcostimulatory moleculesen
dc.subjectimmunosenescenceen
dc.titleSirt6 regulates dendritic cell differentiation, maturation, and functionen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalAging (Albany NY)en
dash.depositing.authorMostoslavsky, Raulen_US
dc.date.available2016-04-01T15:47:31Z
dash.authorsorderedfalse
dash.contributor.affiliatedMostoslavsky, Raul


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