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Blood, 26 March 2009, Vol. 113, No. 13, pp. 2906-2913. Prepublished online as a Blood First Edition Paper on January 22, 2009; DOI 10.1182/blood-2008-08-176354. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2008-08-176354v1 113/13/2906    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Wang, T. Articles by Whartenby, K. A. Search for Related Content PubMed PubMed Citation Articles by Wang, T. Articles by Whartenby, K. A. Related Collections Immunobiology Gene Therapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  GENE THERAPY Inhibition of activation-induced death of dendritic cells and enhancement of vaccine efficacy via blockade of MINOR Tianhong Wang1, Qiong Jiang2, Camie Chan3,4, Kevin S. Gorski5, Erin McCadden1, David Kardian1, Drew Pardoll1, and Katharine A. Whartenby1 1 Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD; 2 SA Biosciences, Frederick, MD; 3 Department of Cell Biology and Human Anatomy, School of Medicine, University of California–Davis; 4 Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children Northern California, Sacramento; and 5 Amgen, Thousand Oaks, CA Activation 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 apoptosis in DCs and suggest that this approach may be a novel means to improve the potency of ex vivo–generated DC vaccines. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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