NK CELL TOLERANCE IN LIVER TRANSPLANTATION IS RELATED TO STAT4 DOWNREGULATION
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ABSTRACT: Liver transplantation (LT) is a definitive treatment for end-stage liver disease and hepatocellular cancer. As donor-recipient HLA matching is not employed, there is potential for natural killer (NK) cell-mediated alloreactivity. Here we report that recipient NK cells exhibit a downregulated phenotype with reduced expression of activating receptors NKp30 and NKp46. We found associated hypofunctionality, with impaired NK cell cytotoxicity, degranulation and IFN-gamma production. Gene expression analysis using microarray and quantitative PCR identified significant downregulation of STAT-4 in LT with associated reduction in miR-155, a microRNA target of STAT-4 and a key regulator of NK differentiation. These data indicate that LT induces recipient NK cell tolerance through altered peripheral maturation at a step prior to the acquisition of inhibitory receptors for HLA class I.
ORGANISM(S): Homo sapiens
SUBMITTER: Khaleel Jamil
PROVIDER: E-MTAB-2132 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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