schliessen

Filtern

 

Bibliotheken

Inhibition of p300 impairs Foxp3⁺ T regulatory cell function and promotes antitumor immunity.

Forkhead box P3 (Foxp3) super(+) T regulatory (T sub(reg)) cells maintain immune homeostasis and limit autoimmunity but can also curtail host immune responses to various types of tumors. Foxp3 super(+) T sub(reg) cells are therefore considered promising targets to enhance antitumor immunity, and app... Full description

Journal Title: Nature medicine September 2013, Vol.19(9), pp.1173-1177
Main Author: Liu, Yujie
Other Authors: Wang, Liqing , Predina, Jarrod , Han, Rongxiang , Beier, Ulf H , Wang, Liang-Chuan S , Kapoor, Veena , Bhatti, Tricia R , Akimova, Tatiana , Singhal, Sunil , Brindle, Paul K , Cole, Philip A , Albelda, Steven M , Hancock, Wayne W
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: E-ISSN: 1546-170X ; DOI: 10.1038/nm.3286
Link: http://search.proquest.com/docview/1431295249/?pq-origsite=primo
Zum Text:
SendSend as email Add to Book BagAdd to Book Bag
Staff View
recordid: proquest1431295249
title: Inhibition of p300 impairs Foxp3⁺ T regulatory cell function and promotes antitumor immunity.
format: Article
creator:
  • Liu, Yujie
  • Wang, Liqing
  • Predina, Jarrod
  • Han, Rongxiang
  • Beier, Ulf H
  • Wang, Liang-Chuan S
  • Kapoor, Veena
  • Bhatti, Tricia R
  • Akimova, Tatiana
  • Singhal, Sunil
  • Brindle, Paul K
  • Cole, Philip A
  • Albelda, Steven M
  • Hancock, Wayne W
subjects:
  • Animals–Immunology
  • Cd8-Positive T-Lymphocytes–Metabolism
  • Cell Line–Metabolism
  • Cell Proliferation–Immunology
  • Chromatin–Immunology
  • Female–Metabolism
  • Forkhead Transcription Factors–Antagonists & Inhibitors
  • Hek293 Cells–Metabolism
  • Humans–Metabolism
  • Immunotherapy–Metabolism
  • Male–Metabolism
  • Mice–Metabolism
  • Mice, Inbred Balb C–Metabolism
  • Mice, Inbred C57bl–Metabolism
  • Mice, Knockout–Metabolism
  • Neoplasms–Metabolism
  • T-Lymphocytes, Regulatory–Metabolism
  • P300-Cbp Transcription Factors–Metabolism
  • Chromatin
  • Forkhead Transcription Factors
  • Foxp3 Protein, Mouse
  • P300-Cbp Transcription Factors
ispartof: Nature medicine, September 2013, Vol.19(9), pp.1173-1177
description: Forkhead box P3 (Foxp3) super(+) T regulatory (T sub(reg)) cells maintain immune homeostasis and limit autoimmunity but can also curtail host immune responses to various types of tumors. Foxp3 super(+) T sub(reg) cells are therefore considered promising targets to enhance antitumor immunity, and approaches for their therapeutic modulation are being developed. However, although studies showing that experimentally depleting Foxp3 super(+) T sub(reg) cells can enhance antitumor responses provide proof of principle, these studies lack clear translational potential and have various shortcomings. Histone/protein acetyltransferases (HATs) promote chromatin accessibility, gene transcription and the function of multiple transcription factors and nonhistone proteins. We now report that conditional deletion or pharmacologic inhibition of one HAT, p300 (also known as Ep300 or KAT3B), in Foxp3 super(+) T sub(reg) cells increased T cell receptor-induced apoptosis in T sub(reg) cells, impaired T sub(reg) cell suppressive function and peripheral T sub(reg) cell induction, and limited tumor growth in immunocompetent but not in immunodeficient mice. Our data thereby demonstrate that p300 is important for Foxp3 super(+) T sub(reg) cell function and homeostasis in vivo and in vitro, and identify mechanisms by which appropriate small-molecule inhibitors can diminish T sub(reg) cell function without overtly impairing T effector cell responses or inducing autoimmunity. Collectively, these data suggest a new approach for cancer immunotherapy.
language: eng
source:
identifier: E-ISSN: 1546-170X ; DOI: 10.1038/nm.3286
fulltext: fulltext
issn:
  • 1546170X
  • 1546-170X
url: Link


@attributes
ID63147872
RANK0.07
NO1
SEARCH_ENGINEprimo_central_multiple_fe
SEARCH_ENGINE_TYPEPrimo Central Search Engine
LOCALfalse
PrimoNMBib
record
control
sourcerecordid1431295249
sourceidproquest
recordidTN_proquest1431295249
sourcesystemPC
pqid1431295249
galeid344208271
display
typearticle
titleInhibition of p300 impairs Foxp3⁺ T regulatory cell function and promotes antitumor immunity.
creatorLiu, Yujie ; Wang, Liqing ; Predina, Jarrod ; Han, Rongxiang ; Beier, Ulf H ; Wang, Liang-Chuan S ; Kapoor, Veena ; Bhatti, Tricia R ; Akimova, Tatiana ; Singhal, Sunil ; Brindle, Paul K ; Cole, Philip A ; Albelda, Steven M ; Hancock, Wayne W
contributorLiu, Yujie (correspondence author) ; Liu, Yujie (record owner)
ispartofNature medicine, September 2013, Vol.19(9), pp.1173-1177
identifierE-ISSN: 1546-170X ; DOI: 10.1038/nm.3286
subjectAnimals–Immunology ; Cd8-Positive T-Lymphocytes–Metabolism ; Cell Line–Metabolism ; Cell Proliferation–Immunology ; Chromatin–Immunology ; Female–Metabolism ; Forkhead Transcription Factors–Antagonists & Inhibitors ; Hek293 Cells–Metabolism ; Humans–Metabolism ; Immunotherapy–Metabolism ; Male–Metabolism ; Mice–Metabolism ; Mice, Inbred Balb C–Metabolism ; Mice, Inbred C57bl–Metabolism ; Mice, Knockout–Metabolism ; Neoplasms–Metabolism ; T-Lymphocytes, Regulatory–Metabolism ; P300-Cbp Transcription Factors–Metabolism ; Chromatin ; Forkhead Transcription Factors ; Foxp3 Protein, Mouse ; P300-Cbp Transcription Factors
languageeng
source
descriptionForkhead box P3 (Foxp3) super(+) T regulatory (T sub(reg)) cells maintain immune homeostasis and limit autoimmunity but can also curtail host immune responses to various types of tumors. Foxp3 super(+) T sub(reg) cells are therefore considered promising targets to enhance antitumor immunity, and approaches for their therapeutic modulation are being developed. However, although studies showing that experimentally depleting Foxp3 super(+) T sub(reg) cells can enhance antitumor responses provide proof of principle, these studies lack clear translational potential and have various shortcomings. Histone/protein acetyltransferases (HATs) promote chromatin accessibility, gene transcription and the function of multiple transcription factors and nonhistone proteins. We now report that conditional deletion or pharmacologic inhibition of one HAT, p300 (also known as Ep300 or KAT3B), in Foxp3 super(+) T sub(reg) cells increased T cell receptor-induced apoptosis in T sub(reg) cells, impaired T sub(reg) cell suppressive function and peripheral T sub(reg) cell induction, and limited tumor growth in immunocompetent but not in immunodeficient mice. Our data thereby demonstrate that p300 is important for Foxp3 super(+) T sub(reg) cell function and homeostasis in vivo and in vitro, and identify mechanisms by which appropriate small-molecule inhibitors can diminish T sub(reg) cell function without overtly impairing T effector cell responses or inducing autoimmunity. Collectively, these data suggest a new approach for cancer immunotherapy.
version8
lds50peer_reviewed
links
openurl$$Topenurl_article
openurlfulltext$$Topenurlfull_article
backlink$$Uhttp://search.proquest.com/docview/1431295249/?pq-origsite=primo$$EView_record_in_ProQuest_(subscribers_only)
search
creatorcontrib
0Liu, Yujie
1Wang, Liqing
2Predina, Jarrod
3Han, Rongxiang
4Beier, Ulf H
5Wang, Liang-Chuan S
6Kapoor, Veena
7Bhatti, Tricia R
8Akimova, Tatiana
9Singhal, Sunil
10Brindle, Paul K
11Cole, Philip A
12Albelda, Steven M
13Hancock, Wayne W
titleInhibition of p300 impairs Foxp3⁺ T regulatory cell function and promotes antitumor immunity.
subject
0Animals–Immunology
1Cd8-Positive T-Lymphocytes–Metabolism
2Cell Line–Metabolism
3Cell Proliferation–Immunology
4Chromatin–Immunology
5Female–Metabolism
6Forkhead Transcription Factors–Antagonists & Inhibitors
7Hek293 Cells–Metabolism
8Humans–Metabolism
9Immunotherapy–Metabolism
10Male–Metabolism
11Mice–Metabolism
12Mice, Inbred Balb C–Metabolism
13Mice, Inbred C57bl–Metabolism
14Mice, Knockout–Metabolism
15Neoplasms–Metabolism
16T-Lymphocytes, Regulatory–Metabolism
17P300-Cbp Transcription Factors–Metabolism
18Chromatin
19Forkhead Transcription Factors
20Foxp3 Protein, Mouse
21P300-Cbp Transcription Factors
22GSE47989
23GEO
general
0English
110.1038/nm.3286
2MEDLINE (ProQuest)
3ProQuest Biological Science Collection
4ProQuest Natural Science Collection
5ProQuest SciTech Collection
6Biological Science Database
7Natural Science Collection
8SciTech Premium Collection
9Health Research Premium Collection
10Health Research Premium Collection (Alumni edition)
11Biological Science Index (ProQuest)
sourceidproquest
recordidproquest1431295249
issn
01546170X
11546-170X
rsrctypearticle
creationdate2013
addtitleNature medicine
searchscope
01007527
11007944
21009130
310000004
410000038
510000050
610000120
710000159
810000238
910000253
1010000260
1110000270
1210000271
1310000302
1410000350
15proquest
scope
01007527
11007944
21009130
310000004
410000038
510000050
610000120
710000159
810000238
910000253
1010000260
1110000270
1210000271
1310000302
1410000350
15proquest
lsr43
01007527false
11007944false
21009130false
310000004false
410000038false
510000050false
610000120false
710000159false
810000238false
910000253false
1010000260false
1110000270false
1210000271false
1310000302false
1410000350false
contributorLiu, Yujie
startdate20130901
enddate20130901
citationpf 1173 pt 1177 vol 19 issue 9
lsr30VSR-Enriched:[issn, galeid, description, pqid]
sort
titleInhibition of p300 impairs Foxp3⁺ T regulatory cell function and promotes antitumor immunity.
authorLiu, Yujie ; Wang, Liqing ; Predina, Jarrod ; Han, Rongxiang ; Beier, Ulf H ; Wang, Liang-Chuan S ; Kapoor, Veena ; Bhatti, Tricia R ; Akimova, Tatiana ; Singhal, Sunil ; Brindle, Paul K ; Cole, Philip A ; Albelda, Steven M ; Hancock, Wayne W
creationdate20130901
lso0120130901
facets
frbrgroupid6774504912960179511
frbrtype5
newrecords20181218
languageeng
creationdate2013
topic
0Animals–Immunology
1Cd8-Positive T-Lymphocytes–Metabolism
2Cell Line–Metabolism
3Cell Proliferation–Immunology
4Chromatin–Immunology
5Female–Metabolism
6Forkhead Transcription Factors–Antagonists & Inhibitors
7Hek293 Cells–Metabolism
8Humans–Metabolism
9Immunotherapy–Metabolism
10Male–Metabolism
11Mice–Metabolism
12Mice, Inbred Balb C–Metabolism
13Mice, Inbred C57bl–Metabolism
14Mice, Knockout–Metabolism
15Neoplasms–Metabolism
16T-Lymphocytes, Regulatory–Metabolism
17P300-Cbp Transcription Factors–Metabolism
18Chromatin
19Forkhead Transcription Factors
20Foxp3 Protein, Mouse
21P300-Cbp Transcription Factors
collection
0MEDLINE (ProQuest)
1ProQuest Biological Science Collection
2ProQuest Natural Science Collection
3ProQuest SciTech Collection
4Biological Science Database
5Natural Science Collection
6SciTech Premium Collection
7Health Research Premium Collection
8Health Research Premium Collection (Alumni edition)
9Biological Science Index (ProQuest)
prefilterarticles
rsrctypearticles
creatorcontrib
0Liu, Yujie
1Wang, Liqing
2Predina, Jarrod
3Han, Rongxiang
4Beier, Ulf H
5Wang, Liang-Chuan S
6Kapoor, Veena
7Bhatti, Tricia R
8Akimova, Tatiana
9Singhal, Sunil
10Brindle, Paul K
11Cole, Philip A
12Albelda, Steven M
13Hancock, Wayne W
jtitleNature medicine
toplevelpeer_reviewed
delivery
delcategoryRemote Search Resource
fulltextfulltext
addata
aulast
0Liu
1Wang
2Predina
3Han
4Beier
5Kapoor
6Bhatti
7Akimova
8Singhal
9Brindle
10Cole
11Albelda
12Hancock
aufirst
0Yujie
1Liqing
2Jarrod
3Rongxiang
4Ulf H
5Liang-Chuan S
6Veena
7Tricia R
8Tatiana
9Sunil
10Paul K
11Philip A
12Steven M
13Wayne W
au
0Liu, Yujie
1Wang, Liqing
2Predina, Jarrod
3Han, Rongxiang
4Beier, Ulf H
5Wang, Liang-Chuan S
6Kapoor, Veena
7Bhatti, Tricia R
8Akimova, Tatiana
9Singhal, Sunil
10Brindle, Paul K
11Cole, Philip A
12Albelda, Steven M
13Hancock, Wayne W
addauLiu, Yujie
atitleInhibition of p300 impairs Foxp3⁺ T regulatory cell function and promotes antitumor immunity.
jtitleNature medicine
risdate20130901
volume19
issue9
spage1173
epage1177
pages1173-1177
eissn1546-170X
formatjournal
genrearticle
ristypeJOUR
doi10.1038/nm.3286
urlhttp://search.proquest.com/docview/1431295249/
issn10788956
date2013-09-01