期刊
GENE THERAPY
卷 16, 期 10, 页码 1245-1259出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/gt.2009.77
关键词
complement receptor; innate immunity; liver; recombinant Adenovirus
类别
资金
- American Heart Association Midwest Affiliate Fellowship [0815660G]
- National Institutes of Health [RO1DK-069884, P01 CA078673]
- MSU Foundation
- Osteopathic Heritage Foundation
Human complement receptors 1 and 2 are well described as important regulators of innate and adaptive immune responses, having pivotal roles in regulating complement activation (CR1) and B-cell maturation/survival. In contrast, the role of the murine homologs of CR1 and CR2 (mCR1/2) have been primarily defined as modulating activation of the adaptive immune system, with very little evidence available about the role of mCR1/2 in regulating the innate immune responses to pathogens. In this paper, we confirm that mCR1/2 plays an important role in regulating both the innate and adaptive immune responses noted after Adenovirus (Ad)-mediated gene transfer. Our results uncovered a novel role of mCR1/2 in downregulating several complement-dependent innate immune responses. We also unveiled the mechanism underlying the complement-dependent induction of neutralizing antibodies to Ad capsids as a CR1/2-dependent phenomenon that correlates with B-cell activation. These results confirm that Ad interactions with the complement system are pivotal in understanding how to maximize the safety or potency of Ad-mediated gene transfer for both gene therapy and vaccine applications. Gene Therapy (2009) 16, 1245-1259; doi: 10.1038/gt.2009.77; published online 25 June 2009
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