Linked Life Data

18443600

Source:http://linkedlifedata.com/resource/pubmed/id/18443600

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2008-6-24
pubmed:abstractText
Recombinant adenoviruses have been used widely for gene therapy due to their high transduction efficiency in vivo. However, the attendant innate immune response to adenoviral vectors has limited their applications for in vivo gene therapy. Recent studies have shown that adenoviruses activate the innate immunity through both Toll-like receptor-dependent (TLR-dependent) and TLR-independent pathways, leading to the production of type I interferons (IFNs) and other inflammatory cytokines. Furthermore, type I IFNs play a pivotal role in innate immune elimination of adenoviral vectors in vivo. It remains to be defined how type I IFNs regulate innate immune clearance of adenoviral vectors. In this study, we showed in vivo that natural killer (NK) cells were activated and accumulated in the liver upon intravenous administration of adenoviral vectors, leading to the loss of adenoviral genome and the reduction of transgene expression. We further demonstrated that type I IFNs were critical for the activation of NK cells. This was achieved by direct action of type I IFNs on NK cells. Overall, our observations reveal a critical role for type I IFN-dependent NK cell activation in innate immune elimination of adenoviral vectors in vivo and may help design effective strategies to improve the outcome of adenovirus-mediated gene therapy.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1525-0024
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
16
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1300-7
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
A critical role for type I IFN-dependent NK cell activation in innate immune elimination of adenoviral vectors in vivo.
pubmed:affiliation
Department of Medicine, Division of Medical Oncology, Duke University Medical Center, Durham, North Carolina 27710, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural