PMID- 31949209
OWN - NLM
STAT- MEDLINE
DCOM- 20201116
LR  - 20211117
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 10
IP  - 1
DP  - 2020 Jan 16
TI  - HDAC10 deletion promotes Foxp3(+) T-regulatory cell function.
PG  - 424
LID - 10.1038/s41598-019-57294-x [doi]
LID - 424
AB  - Foxp3(+) T-regulatory (Treg) cells are capable of suppressing immune responses. 
      Lysine acetylation is a key mechanism of post-translational control of various 
      transcription factors, and when acetylated, Foxp3 is stabilized and 
      transcriptionally active. Therefore, understanding the roles of various 
      histone/protein deacetylases (HDAC) are key to promoting Treg-based 
      immunotherapy. Several of the 11 classical HDAC enzymes are necessary for optimal 
      Treg function while others are dispensable. We investigated the effect of HDAC10 
      in murine Tregs. HDAC10 deletion had no adverse effect on the health of mice, 
      which retained normal CD4(+) and CD8(+) T cell function. However, HDAC10(-/-) 
      Treg exhibited increased suppressive function in vitro and in vivo. C57BL/6 
      Rag1(-/-) mice adoptively transferred with HDAC10(-/-) but not wild Treg, were 
      protected from developing colitis. HDAC10(-/-) but not wild-type mice receiving 
      fully MHC-mismatched cardiac transplants became tolerant and showed long-term 
      allograft survival (>100 d). We conclude that targeting of HDAC10 may be of 
      therapeutic value for inflammatory disorders including colitis and also for 
      transplantation.
FAU - Dahiya, Satinder
AU  - Dahiya S
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, PA, 19104, USA.
FAU - Beier, Ulf H
AU  - Beier UH
AUID- ORCID: 0000-0002-3672-572X
AD  - Division of Nephrology and Department of Pediatrics, Children's Hospital of 
      Philadelphia and University of Pennsylvania, Philadelphia, PA, 19104, USA.
FAU - Wang, Liqing
AU  - Wang L
AUID- ORCID: 0000-0001-7600-6992
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, PA, 19104, USA.
FAU - Han, Rongxiang
AU  - Han R
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, PA, 19104, USA.
FAU - Jiao, Jing
AU  - Jiao J
AD  - Division of Nephrology and Department of Pediatrics, Children's Hospital of 
      Philadelphia and University of Pennsylvania, Philadelphia, PA, 19104, USA.
FAU - Akimova, Tatiana
AU  - Akimova T
AUID- ORCID: 0000-0003-2767-8762
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, PA, 19104, USA.
FAU - Angelin, Alessia
AU  - Angelin A
AD  - Center for Mitochondrial and Epigenomic Medicine, Children's Hospital of 
      Philadelphia, Philadelphia, PA, 19104, USA.
FAU - Wallace, Douglas C
AU  - Wallace DC
AUID- ORCID: 0000-0002-7480-8278
AD  - Center for Mitochondrial and Epigenomic Medicine, Children's Hospital of 
      Philadelphia, Philadelphia, PA, 19104, USA.
FAU - Hancock, Wayne W
AU  - Hancock WW
AUID- ORCID: 0000-0002-7211-5291
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, PA, 19104, USA. 
      whancock@pennmedicine.upenn.edu.
LA  - eng
GR  - R01 MH108592/MH/NIMH NIH HHS/United States
GR  - R56 AI095276/AI/NIAID NIH HHS/United States
GR  - R01 OD010944/OD/NIH HHS/United States
GR  - R01 AI123241/AI/NIAID NIH HHS/United States
GR  - R01 NS021328/NS/NINDS NIH HHS/United States
GR  - P01 AI073489/AI/NIAID NIH HHS/United States
GR  - K08 AI095353/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20200116
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (FOXP3 protein, human)
RN  - 0 (Forkhead Transcription Factors)
SB  - IM
MH  - Animals
MH  - Colitis/genetics/immunology
MH  - Forkhead Transcription Factors/*metabolism
MH  - *Gene Deletion
MH  - HEK293 Cells
MH  - Heart Transplantation/adverse effects
MH  - Humans
MH  - Mice
MH  - T-Lymphocytes, Regulatory/*cytology
MH  - Transplantation Tolerance/genetics
PMC - PMC6965082
COIS- The authors declare no competing interests.
EDAT- 2020/01/18 06:00
MHDA- 2020/11/18 06:00
PMCR- 2020/01/16
CRDT- 2020/01/18 06:00
PHST- 2019/09/11 00:00 [received]
PHST- 2019/12/24 00:00 [accepted]
PHST- 2020/01/18 06:00 [entrez]
PHST- 2020/01/18 06:00 [pubmed]
PHST- 2020/11/18 06:00 [medline]
PHST- 2020/01/16 00:00 [pmc-release]
AID - 10.1038/s41598-019-57294-x [pii]
AID - 57294 [pii]
AID - 10.1038/s41598-019-57294-x [doi]
PST - epublish
SO  - Sci Rep. 2020 Jan 16;10(1):424. doi: 10.1038/s41598-019-57294-x.