PMID- 30605226
OWN - NLM
STAT- MEDLINE
DCOM- 20200511
LR  - 20200911
IS  - 1938-3673 (Electronic)
IS  - 0741-5400 (Print)
IS  - 0741-5400 (Linking)
VI  - 106
IP  - 2
DP  - 2019 Aug
TI  - Sirtuin-1 in immunotherapy: A Janus-headed target.
PG  - 337-343
LID - 10.1002/JLB.2RU1118-422R [doi]
AB  - Sirtuin-1 (Sirt1), a member of the NAD-dependent sirtuin family of 
      histone/protein deacetylases (HDAC), is an important target for immunotherapy due 
      to its role in deacetylating the transcription factors Foxp3 and thymic retinoid 
      acid receptor related orphan receptor gamma (RORgammat). Sirt1 inhibition can 
      increase Foxp3 acetylation and promote the production and functions of Foxp3(+) 
      T-regulatory (Treg) cells, whereas the acetylation of RORgammat decreases its 
      transcriptional activity DNA binding and decreases the differentiation of 
      proinflammatory Th17 cells. Pharmacologic inhibitors of Sirt1 increase allograft 
      survival and decrease autoimmune colitis and experimental allergic 
      encephalomyelitis. However, in contrast to its role in T cells, Sirt1 has 
      anti-inflammatory effects in myeloid cells, and, context dependent, in Th17 
      cells. Here, inhibition of Sirt1 can have proinflammatory effects. In addition to 
      effects arising from the central role of Sirt1 in cellular metabolism and 
      NAD-dependent reactions, such proinflammatory effects further complicate the 
      potential of Sirt1 for therapeutic immunosuppression. This review aims to 
      reconcile the opposing literature on pro- and anti-inflammatory effects of Sirt1, 
      provides an overview of the role of Sir1 in the immune system, and discusses the 
      pros and cons associated with inhibiting Sirt1 for control of inflammation and 
      immune responses.
CI  - (c)2019 Society for Leukocyte Biology.
FAU - Chadha, Sakshum
AU  - Chadha S
AD  - Division of Nephrology, Department of Pediatrics, Children's Hospital of 
      Philadelphia, Philadelphia, Pennsylvania, USA.
FAU - Wang, Liqing
AU  - Wang L
AD  - Division of Transplant Immunology, Department of Pathology and Laboratory 
      Medicine, and Biesecker Center for Pediatric Liver Disease, Children's Hospital 
      of Philadelphia and University of Pennsylvania, Philadelphia, Pennsylvania, USA.
FAU - Hancock, Wayne W
AU  - Hancock WW
AD  - Division of Transplant Immunology, Department of Pathology and Laboratory 
      Medicine, and Biesecker Center for Pediatric Liver Disease, Children's Hospital 
      of Philadelphia and University of Pennsylvania, Philadelphia, Pennsylvania, USA.
FAU - Beier, Ulf H
AU  - Beier UH
AD  - Division of Nephrology, Department of Pediatrics, Children's Hospital of 
      Philadelphia, Philadelphia, Pennsylvania, USA.
LA  - eng
GR  - K08 AI095353/AI/NIAID NIH HHS/United States
GR  - P01 AI073489/AI/NIAID NIH HHS/United States
GR  - R56 AI095276/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20190103
PL  - England
TA  - J Leukoc Biol
JT  - Journal of leukocyte biology
JID - 8405628
RN  - 0 (Immunologic Factors)
RN  - 0 (Immunosuppressive Agents)
RN  - 0U46U6E8UK (NAD)
RN  - EC 3.5.1.- (Sirtuin 1)
SB  - IM
MH  - Animals
MH  - Disease Susceptibility
MH  - Energy Metabolism
MH  - Gene Expression Regulation
MH  - Humans
MH  - Immune System/immunology/metabolism
MH  - Immunologic Factors/pharmacology/*therapeutic use
MH  - Immunosuppressive Agents/pharmacology/therapeutic use
MH  - *Immunotherapy/methods
MH  - Myeloid Cells/immunology/metabolism
MH  - NAD/metabolism
MH  - Sirtuin 1/*genetics/*metabolism
MH  - T-Lymphocyte Subsets/immunology/metabolism
PMC - PMC7477756
MID - NIHMS1620792
OTO - NOTNLM
OT  - Foxp3
OT  - T cells
OT  - Treg
OT  - immunosuppression
OT  - p65
COIS- Conflict of Interest Disclosure The authors declare that the research was 
      conducted in the absence of any commercial or financial relationships that could 
      be construed as a potential conflict of interest.
EDAT- 2019/01/04 06:00
MHDA- 2020/05/12 06:00
PMCR- 2020/09/08
CRDT- 2019/01/04 06:00
PHST- 2018/11/05 00:00 [received]
PHST- 2018/12/13 00:00 [revised]
PHST- 2018/12/16 00:00 [accepted]
PHST- 2019/01/04 06:00 [pubmed]
PHST- 2020/05/12 06:00 [medline]
PHST- 2019/01/04 06:00 [entrez]
PHST- 2020/09/08 00:00 [pmc-release]
AID - 10.1002/JLB.2RU1118-422R [doi]
PST - ppublish
SO  - J Leukoc Biol. 2019 Aug;106(2):337-343. doi: 10.1002/JLB.2RU1118-422R. Epub 2019 
      Jan 3.