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|Title:||Toll-like receptor 3 and 7/8 function is impaired in hepatitis C rapid fibrosis progression post-liver transplantation.|
|Authors:||Howell, Jessica;Sawhney, R;Skinner, N;Gow, Paul J;Angus, Peter W;Ratnam, D;Visvanathan, K|
|Affiliation:||Liver Transplant Unit, Austin Hospital, Department of Medicine, University of Melbourne, Australia. firstname.lastname@example.org|
|Citation:||American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons 2013; 13(4): 943-53|
|Abstract:||Recurrence of hepatitis C (HCV) postliver transplant is universal, with a subgroup developing rapid hepatic fibrosis. Toll-like receptors (TLRs) are critical to innate antiviral responses and HCV alters TLR function to evade immune clearance. Whether TLRs play a role in rapid HCV recurrence posttransplant is unknown. We stimulated peripheral blood mononuclear cells (PBMCs) from 70 patients with HCV postliver transplant with TLR subclass-specific ligands and measured cytokine production, TLR expression and NK cell function. Rate of fibrosis progression was calculated using posttransplant liver biopsies graded by Metavir scoring (F0-4; R=fibrosis stage/year posttransplant; rapid fibrosis defined as >0.4 units/year). Thirty of 70 (43%) patients had rapid fibrosis progression. PBMCs from HCV rapid-fibrosers produced less IFNα with TLR7/8 stimulation (p=0.039), less IL-6 at baseline (p=0.027) and with TLR3 stimulation (p=0.008) and had lower TLR3-mediated monocyte IL-6 production (p=0.028) compared with HCV slow fibrosers. TLR7/8-mediated NKCD56 dim cell secretion of IFNγ was impaired in HCV rapid fibrosis (p=0.006) independently of IFNα secretion and TLR7/8 expression, while cytotoxicity remained preserved. Impaired TLR3 and TLR7/8-mediated cytokine responses may contribute to aggressive HCV recurrence postliver transplantation through impaired immune control of HCV and subsequent activation of fibrogenesis.|
|Internal ID Number:||23425350|
Killer Cells, Natural.cytology
Toll-Like Receptor 3.metabolism
Toll-Like Receptor 7.metabolism
Toll-Like Receptor 8.metabolism
|Appears in Collections:||Journal articles|
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