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Lipidoid Nanoparticles Containing PD-L1 siRNA Delivered In Vivo Enter Kupffer Cells and Enhance NK and CD8(+) T Cell-mediated Hepatic Antiviral Immunity.

Abstract：

:Effective clinical application of antiviral immunotherapies necessitates enhancing the functional state of natural killer (NK) and CD8(+) T cells. An important mechanism for the establishment of viral persistence in the liver is the activation of the PD-1/PD-L1 inhibitory pathway. To examine the role of hepatic myeloid PD-L1 expression during viral infection, we determined the magnitude and quality of antiviral immune responses by administering PD-L1 short-interfering RNA (siRNA) encapsulated in lipidoid nanoparticles (LNP) in mice. Our studies indicate that Kupffer cells (KC) preferentially engulfed PD-L1 LNP within a short period of time and silenced Pdl1 during adenovirus and MCMV infection leading to enhanced NK and CD8(+) T cell intrahepatic accumulation, effector function (interferon (IFN)-γ and granzyme B (GrB) production), CD8(+) T cell-mediated viral clearance, and memory. Our results demonstrate that PD-L1 knockdown on KCs is central in determining the outcome of liver viral infections, and they represent a new class of gene therapy.Molecular Therapy - Nucleic Acids (2013) 2, e72; doi:10.1038/mtna.2012.63; published online 19 February 2013.

journal_name

Mol Ther Nucleic Acids

journal_title

Molecular therapy. Nucleic acids

authors

Dolina JS,Sung SS,Novobrantseva TI,Nguyen TM,Hahn YS

doi

10.1038/mtna.2012.63

subject

Has Abstract

pub_date

2013-02-19 00:00:00

pages

e72

issn

2162-2531

pii

mtna201263

journal_volume

2

pub_type

杂志文章

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