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Article: Inhibition of activation-induced death of dendritic cells and enhancement of vaccine efficacy via blockade of MINOR

TitleInhibition of activation-induced death of dendritic cells and enhancement of vaccine efficacy via blockade of MINOR
Authors
KeywordsMolecular Sequence Numbers
Issue Date2009
PublisherAmerican Society of Hematology. The Journal's web site is located at http://bloodjournal.hematologylibrary.org/
Citation
Blood, 2009, v. 113 n. 13, p. 2906-2913 How to Cite?
AbstractActivation of dendritic cells (DCs) leads to cell maturation, which is accompanied by a regulated pattern of gene expression changes. Two significant and contradictory consequences of DC activation are that, although activation is necessary for maximal T-cell stimulation, it also leads to the initiation of gene expression that results ultimately in cell death. We have identified a gene, MINOR (mitogen- inducible nuclear orphan receptor), that becomes highly up-regulated on activation and whose expression leads to apoptosis in mature DCs. MINOR is a member of the Nur77 family of nuclear orphan receptors, which includes Nur77 and Nurr1. Although Nur77 and Nurr1 are expressed in macrophages and DCs, their expression levels do not change on DC activation. We thus tested the hypothesis that induction of MINOR would lead to an activation- induced cell death in DCs and that its inhibition would increase the lifespan of DCs and improve their vaccine efficacy. To block natural expression of MINOR by DCs, we generated a lentiviral vector that expresses a small interfering RNA. Our results indicate that blockade of MINOR expression dramatically decreases apo- ptosis in DCs and suggest that this approach may be a novel means to improve the potency of ex vivo-generated DC vaccines. © 2009 by The American Society of Hematology.
Persistent Identifierhttp://hdl.handle.net/10722/90966
ISSN
2014 Impact Factor: 10.452
2014 SCImago Journal Rankings: 5.246
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
National Cancer InstituteR01-CA111989
Funding Information:

This work was supported by the National Cancer Institute ( Bethesda, MD; R01-CA111989).

References

 

DC FieldValueLanguage
dc.contributor.authorWang, Ten_HK
dc.contributor.authorJiang, Qen_HK
dc.contributor.authorChan, Cen_HK
dc.contributor.authorGorski, KSen_HK
dc.contributor.authorMcCadden, Een_HK
dc.contributor.authorKardian, Den_HK
dc.contributor.authorPardoll, Den_HK
dc.contributor.authorWhartenby, KAen_HK
dc.date.accessioned2010-09-17T10:11:03Z-
dc.date.available2010-09-17T10:11:03Z-
dc.date.issued2009en_HK
dc.identifier.citationBlood, 2009, v. 113 n. 13, p. 2906-2913en_HK
dc.identifier.issn0006-4971en_HK
dc.identifier.urihttp://hdl.handle.net/10722/90966-
dc.description.abstractActivation of dendritic cells (DCs) leads to cell maturation, which is accompanied by a regulated pattern of gene expression changes. Two significant and contradictory consequences of DC activation are that, although activation is necessary for maximal T-cell stimulation, it also leads to the initiation of gene expression that results ultimately in cell death. We have identified a gene, MINOR (mitogen- inducible nuclear orphan receptor), that becomes highly up-regulated on activation and whose expression leads to apoptosis in mature DCs. MINOR is a member of the Nur77 family of nuclear orphan receptors, which includes Nur77 and Nurr1. Although Nur77 and Nurr1 are expressed in macrophages and DCs, their expression levels do not change on DC activation. We thus tested the hypothesis that induction of MINOR would lead to an activation- induced cell death in DCs and that its inhibition would increase the lifespan of DCs and improve their vaccine efficacy. To block natural expression of MINOR by DCs, we generated a lentiviral vector that expresses a small interfering RNA. Our results indicate that blockade of MINOR expression dramatically decreases apo- ptosis in DCs and suggest that this approach may be a novel means to improve the potency of ex vivo-generated DC vaccines. © 2009 by The American Society of Hematology.en_HK
dc.languageengen_HK
dc.publisherAmerican Society of Hematology. The Journal's web site is located at http://bloodjournal.hematologylibrary.org/en_HK
dc.relation.ispartofBlooden_HK
dc.subjectMolecular Sequence Numbersen_HK
dc.titleInhibition of activation-induced death of dendritic cells and enhancement of vaccine efficacy via blockade of MINORen_HK
dc.typeArticleen_HK
dc.identifier.emailChan, C:camchan@hku.hken_HK
dc.identifier.authorityChan, C=rp01311en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1182/blood-2008-08-176354en_HK
dc.identifier.pmid19164597en_HK
dc.identifier.pmcidPMC2662637-
dc.identifier.scopuseid_2-s2.0-63849118531en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-63849118531&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume113en_HK
dc.identifier.issue13en_HK
dc.identifier.spage2906en_HK
dc.identifier.epage2913en_HK
dc.identifier.eissn1528-0020-
dc.identifier.isiWOS:000264559000009-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridWang, T=36710844300en_HK
dc.identifier.scopusauthoridJiang, Q=36939693500en_HK
dc.identifier.scopusauthoridChan, C=12240386600en_HK
dc.identifier.scopusauthoridGorski, KS=36668518300en_HK
dc.identifier.scopusauthoridMcCadden, E=9435230300en_HK
dc.identifier.scopusauthoridKardian, D=9432747400en_HK
dc.identifier.scopusauthoridPardoll, D=7005961020en_HK
dc.identifier.scopusauthoridWhartenby, KA=35482193700en_HK

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