PMID- 26761436
OWN - NLM
STAT- MEDLINE
DCOM- 20161213
LR  - 20181113
IS  - 1945-4589 (Electronic)
IS  - 1945-4589 (Linking)
VI  - 8
IP  - 1
DP  - 2016 Jan
TI  - Sirt6 regulates dendritic cell differentiation, maturation, and function.
PG  - 34-49
AB  - Dendritic 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-alpha 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.
FAU - Lasiglie, Denise
AU  - Lasiglie D
AD  - Department of Internal Medicine, University of Genoa, 16132 Genoa, Italy.
FAU - Boero, Silvia
AU  - Boero S
AD  - The Istituto di Ricovero e Cura a Carattere Scientifico Azienda Ospedaliera 
      Universitaria San Martino-Istituto Scientifico Tumori, Istituto Nazionale per la 
      Ricerca sul Cancro, 16132 Genoa, Italy.
FAU - Bauer, Inga
AU  - Bauer I
AD  - Department of Internal Medicine, University of Genoa, 16132 Genoa, Italy.
FAU - Morando, Sara
AU  - Morando S
AD  - Department of Neurology, Rehabilitation, Ophthalmology, Genetics, Maternal and 
      Child Health, University of Genoa, 16100 Genoa, Italy.
FAU - Damonte, Patrizia
AU  - Damonte P
AD  - Department of Internal Medicine, University of Genoa, 16132 Genoa, Italy.
FAU - Cea, Michele
AU  - Cea M
AD  - Department of Internal Medicine, University of Genoa, 16132 Genoa, Italy.
FAU - Monacelli, Fiammetta
AU  - Monacelli F
AD  - Department of Internal Medicine, University of Genoa, 16132 Genoa, Italy.
AD  - The Istituto di Ricovero e Cura a Carattere Scientifico Azienda Ospedaliera 
      Universitaria San Martino-Istituto Scientifico Tumori, Istituto Nazionale per la 
      Ricerca sul Cancro, 16132 Genoa, Italy.
FAU - Odetti, Patrizio
AU  - Odetti P
AD  - Department of Internal Medicine, University of Genoa, 16132 Genoa, Italy.
AD  - The Istituto di Ricovero e Cura a Carattere Scientifico Azienda Ospedaliera 
      Universitaria San Martino-Istituto Scientifico Tumori, Istituto Nazionale per la 
      Ricerca sul Cancro, 16132 Genoa, Italy.
FAU - Ballestrero, Alberto
AU  - Ballestrero A
AD  - Department of Internal Medicine, University of Genoa, 16132 Genoa, Italy.
AD  - The Istituto di Ricovero e Cura a Carattere Scientifico Azienda Ospedaliera 
      Universitaria San Martino-Istituto Scientifico Tumori, Istituto Nazionale per la 
      Ricerca sul Cancro, 16132 Genoa, Italy.
FAU - Uccelli, Antonio
AU  - Uccelli A
AD  - The Istituto di Ricovero e Cura a Carattere Scientifico Azienda Ospedaliera 
      Universitaria San Martino-Istituto Scientifico Tumori, Istituto Nazionale per la 
      Ricerca sul Cancro, 16132 Genoa, Italy.
AD  - Department of Neurology, Rehabilitation, Ophthalmology, Genetics, Maternal and 
      Child Health, University of Genoa, 16100 Genoa, Italy.
FAU - Mostoslavsky, Raul
AU  - Mostoslavsky R
AD  - The Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, 
      MA 02114 USA.
FAU - Poggi, Alessandro
AU  - Poggi A
AD  - The Istituto di Ricovero e Cura a Carattere Scientifico Azienda Ospedaliera 
      Universitaria San Martino-Istituto Scientifico Tumori, Istituto Nazionale per la 
      Ricerca sul Cancro, 16132 Genoa, Italy.
FAU - Nencioni, Alessio
AU  - Nencioni A
AD  - Department of Internal Medicine, University of Genoa, 16132 Genoa, Italy.
AD  - The Istituto di Ricovero e Cura a Carattere Scientifico Azienda Ospedaliera 
      Universitaria San Martino-Istituto Scientifico Tumori, Istituto Nazionale per la 
      Ricerca sul Cancro, 16132 Genoa, Italy.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Aging (Albany NY)
JT  - Aging
JID - 101508617
RN  - 0 (Ccr7 protein, mouse)
RN  - 0 (Histocompatibility Antigens Class II)
RN  - 0 (Histone Deacetylase Inhibitors)
RN  - 0 (Interleukin-6)
RN  - 0 (Receptors, CCR7)
RN  - 0 (Toll-Like Receptors)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (interleukin-6, mouse)
RN  - 187348-17-0 (Interleukin-12)
RN  - EC 2.4.2.31 (Sirt6 protein, mouse)
RN  - EC 3.5.1.- (Sirtuins)
SB  - IM
MH  - Animals
MH  - *Cell Differentiation/drug effects
MH  - Cell Lineage
MH  - Cells, Cultured
MH  - Dendritic Cells/drug effects/*enzymology/immunology
MH  - Genotype
MH  - Histocompatibility Antigens Class II/immunology/metabolism
MH  - Histone Deacetylase Inhibitors/pharmacology
MH  - *Immunosenescence/drug effects
MH  - Interleukin-12/immunology/metabolism
MH  - Interleukin-6/immunology/metabolism
MH  - Mice, 129 Strain
MH  - Mice, Inbred BALB C
MH  - Mice, Knockout
MH  - Phenotype
MH  - Receptors, CCR7/immunology/metabolism
MH  - Sirtuins/antagonists & inhibitors/deficiency/genetics/*metabolism
MH  - Toll-Like Receptors/immunology/metabolism
MH  - Tumor Necrosis Factor-alpha/immunology/metabolism
PMC - PMC4761712
OTO - NOTNLM
OT  - Sirt6
OT  - TNF-alpha
OT  - Toll-like receptor ligands
OT  - costimulatory molecules
OT  - dendritic cells
OT  - immunosenescence
COIS- Conflict of interest statement The authors declare no competing financial 
      interests.
EDAT- 2016/01/14 06:00
MHDA- 2016/12/15 06:00
PMCR- 2016/01/01
CRDT- 2016/01/14 06:00
PHST- 2015/11/12 00:00 [received]
PHST- 2015/12/29 00:00 [accepted]
PHST- 2016/01/14 06:00 [entrez]
PHST- 2016/01/14 06:00 [pubmed]
PHST- 2016/12/15 06:00 [medline]
PHST- 2016/01/01 00:00 [pmc-release]
AID - 100870 [pii]
AID - 10.18632/aging.100870 [doi]
PST - ppublish
SO  - Aging (Albany NY). 2016 Jan;8(1):34-49. doi: 10.18632/aging.100870.