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

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TitleInhibition of activation-induced death of dendritic cells and enhancement of vaccine efficacy via blockade of MINOR
AuthorsWang, T2
Jiang, Q5
Chan, C1 4
Gorski, KS3
McCadden, E2
Kardian, D2
Pardoll, D2
Whartenby, KA2 6
KeywordsMolecular Sequence Numbers
Issue Date2009
PublisherAmerican Society of Hematology. The Journal's web site is located at http://bloodjournal.hematologylibrary.org/
CitationBlood, 2009, v. 113 n. 13, p. 2906-2913 [How to Cite?]
DOI: http://dx.doi.org/10.1182/blood-2008-08-176354
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.
ISSN0006-4971
2011 Impact Factor: 9.898
2011 SCImago Journal Rankings: 1.698
DOIhttp://dx.doi.org/10.1182/blood-2008-08-176354
ISI Accession Number IDWOS:000264559000009
Funding AgencyGrant Number
National Cancer InstituteR01-CA111989
Funding Information:

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

PubMed Central IDPMC2662637
ReferencesReferences in Scopus
DC Field
Value
dc.contributor.authorWang, T
dc.contributor.authorJiang, Q
dc.contributor.authorChan, C
dc.contributor.authorGorski, KS
dc.contributor.authorMcCadden, E
dc.contributor.authorKardian, D
dc.contributor.authorPardoll, D
dc.contributor.authorWhartenby, KA
dc.date.accessioned2010-09-17T10:11:03Z
dc.date.available2010-09-17T10:11:03Z
dc.date.issued2009
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.
dc.description.natureLink_to_subscribed_fulltext
dc.identifier.citationBlood, 2009, v. 113 n. 13, p. 2906-2913 [How to Cite?]
DOI: http://dx.doi.org/10.1182/blood-2008-08-176354
dc.identifier.doihttp://dx.doi.org/10.1182/blood-2008-08-176354
dc.identifier.eissn1528-0020
dc.identifier.epage2913
dc.identifier.isiWOS:000264559000009
Funding AgencyGrant Number
National Cancer InstituteR01-CA111989
Funding Information:

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

dc.identifier.issn0006-4971
2011 Impact Factor: 9.898
2011 SCImago Journal Rankings: 1.698
dc.identifier.issue13
dc.identifier.pmcidPMC2662637
dc.identifier.pmid19164597
dc.identifier.scopuseid_2-s2.0-63849118531
dc.identifier.spage2906
dc.identifier.urihttp://hdl.handle.net/10722/90966
dc.identifier.volume113
dc.languageeng
dc.publisherAmerican Society of Hematology. The Journal's web site is located at http://bloodjournal.hematologylibrary.org/
dc.publisher.placeUnited States
dc.relation.ispartofBlood
dc.relation.referencesReferences in Scopus
dc.subjectMolecular Sequence Numbers
dc.titleInhibition of activation-induced death of dendritic cells and enhancement of vaccine efficacy via blockade of MINOR
dc.typeArticle
Author Affiliations
  1. UC Davis School of Medicine
  2. The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
  3. Amgen Incorporated
  4. Shriners Hospitals for Children - Northern California
  5. SA Biosciences
  6. The Johns Hopkins School of Medicine