the role of hepatic nk cells in local tissue remodeling and repair
TRANSCRIPT
The Role of Hepatic NK Cells in Local Tissue Remodeling and Repair
• 25-40% NK cells
The Liver and Hepatic NK Cells
• 25-40% NK cells• Unique phenotype of
hepatic NK cells
The Liver and Hepatic NK Cells
• 25-40% NK cells• Unique phenotype of
hepatic NK cells • Increased cytotoxicity
The Liver and Hepatic NK Cells
• 25-40% NK cells• Unique phenotype of
hepatic NK cells • Increased cytotoxicity• Upregulated cytolytic
molecules
The Liver and Hepatic NK Cells
Hepatic NK cells prevent fibrosis in 2 ways:
• HCV, alcohol• Pro-fibrogenic
cytokines e.g. TGF-β Liver
Injury
• ECM protein deposition
• Scarring
HSC activation • Remodeling of
tissue architecture
• Impaired liver function
FIBROSIS
Hepatic NK cells prevent fibrosis in 2 ways:1. Production of IFN-γ: antifibrotic cytokine
• HCV, alcohol• Pro-fibrogenic
cytokines e.g. TGF-β Liver
Injury
• ECM protein deposition
• Scarring
HSC activation • Remodeling of
tissue architecture
• Impaired organ function
FIBROSIS
Hepatic NK cells prevent fibrosis in 2 ways:1. Production of IFN-γ: antifibrotic cytokine2. Direct killing of early activated hepatic
stellate cells (HSCs)
• HCV, alcohol• Pro-fibrogenic
cytokines e.g. TGF-β Liver
Injury
• ECM protein deposition
• Scarring
HSC activation • Remodeling of
tissue architecture
• Impaired organ function
FIBROSIS
Fibrosis: constant tissue remodeling
and repair
Build up genomic changes and
cellular transformation
Hepatocellular carcinoma
Hepatic NK cells control the progression of HCC by:
Fibrosis: constant tissue remodeling
and repair
Build up genomic changes and
cellular transformation
Hepatocellular carcinoma
Hepatic NK cells control the progression of HCC by:1. Direct targeting and killing of transformed cells
DNA damage response activates NK cells
Fibrosis: constant tissue remodeling
and repair
Build up genomic changes and
cellular transformation
Hepatocellular carcinoma
Hepatic NK cells control the progression of HCC by:1. Direct targeting and killing of transformed cells
DNA damage response activates NK cells2. The production of antitumor cytokines
IFN-γ
Future Directions:NK Cell-Based Immunotherapy• Monoclonal antibodies– Bind target and attract NK cell– Block inhibitory receptors and ligands
• Balance of activating and inhibitory receptors– DNA methylation
• What molecular signals make hepatic NK cells more cytotoxic???– Enhance immune response in other organs