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dc.contributor.authorShrivastava, Shikha
dc.contributor.authorKottilil, Shyam
dc.contributor.authorSherman, Kenneth E.
dc.contributor.authorMasur, Henry
dc.contributor.authorTang, Lydia
dc.date.accessioned2021-10-28T19:00:58Z
dc.date.available2021-10-28T19:00:58Z
dc.date.issued2021-10-14
dc.identifier.urihttp://hdl.handle.net/10713/17011
dc.description.abstractLiver fibrosis is accelerated in patients coinfected with hepatitis C virus and human immunodeficiency virus (HIV), compared with HCV monoinfected patients, although the underlying mechanisms are unknown. We hypothesize that T cells expressing the HIV co-receptor, chemokine receptor 5 (CCR5), preferentially migrate to the inflamed liver and contribute to enhanced fibrogenesis. We compared the peripheral and intrahepatic CCR5 expression on CD4+ and CD8+ T cells in 21 HIV/HCV-coinfected patients with 14 chronic HCV monoinfected patients. Using 12-color flow cytometry, phenotypic and functional characterization of CCR5+ and negative cells pre- and post-stimulation with HCV genotype specific overlapping pooled peptides was conducted. Patients with HIV/HCV coinfection had significantly more CD4+CCR5+ and CD8+CCR5+ T cells in the liver as compared with peripheral blood (p = 0.0001 for both). Compared with patients with HCV monoinfection, patients with HIV/HCV coinfection also had fewer peripheral CD4+CCR5+ and CD8+CCR5+ T cells (p = 0.02, p = 0.001 respectively), but more intrahepatic CD4+CCR5+ and CD8+CCR5+ cells (p = 0.0001 for both). Phenotypic analysis of CCR5+ sorted cells demonstrated an increased expression of markers of exhaustion, senescence, immune activation and liver homing (PD1, CD57, CD38, HLADR, and CXCR3). Post-stimulation with HCV peptides, CCR5+ T cells secreted more proinflammatory and profibrogenic cytokines and chemokines rather than antiviral cytokines. Phenotypic and functional analyses of CCR5+ T cells in HIV/HCV-coinfected patients revealed a pathogenic role for CCR5+ T cells in hepatic fibrogenesis. These cells are functionally proinflammatory, pro-fibrogenic and preferentially accumulate in liver, accelerating fibrosis. These findings suggest that targeting CCR5 may be a therapeutic strategy for be ameliorating liver fibrosis.en_US
dc.description.urihttps://doi.org/10.3390/v13102074en_US
dc.language.isoenen_US
dc.publisherMDPI AGen_US
dc.relation.ispartofVirusesen_US
dc.subjectCCR5en_US
dc.subjectFibrosisen_US
dc.subjectHepatic fibrogenesisen_US
dc.subjectHepatitis Cen_US
dc.subjectHIVen_US
dc.subjectHIV/HCV coinfectionen_US
dc.titleCcr5+ t-cells homed to the liver exhibit inflammatory and profibrogenic signatures in chronic hiv/hcv-coinfected patientsen_US
dc.typeArticleen_US
dc.identifier.doi10.3390/v13102074
dc.source.volume13
dc.source.issue10


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