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Dadun > Depósito Académico > CIMA (Centro de Investigación Médica Aplicada) > Área de Terapia génica y Hepatología > Inmunología hepatitis virales > DA - CIMA - Terapia génica y Hepatología - Inmunología hepatitis virales - Artículos de revista >

Improved dendritic cell-based immunization against hepatitis C virus using peptide inhibitors of interleukin 10
Authors: Diaz-Valdes, N. (Nancy)
Manterola, L. (Lorea)
Belsue, V. (Virginia)
Riezu-Boj, J.I. (José Ignacio)
Larrea, E. (Esther)
Echeverria, I. (Itziar)
Llopiz, D. (Diana)
Lopez-Sagaseta, J. (Jacinto)
Lerat, H. (Hervé)
Pawlotsky, J.M. (Jean-Michel)
Prieto, J. (Jesús)
Lasarte, J.J. (Juan José)
Borras-Cuesta, F. (Francisco)
Sarobe, P. (Pablo)
Keywords: Dendritic Cells/immunology
Hepacivirus/immunology
Interleukin-10/antagonists & inhibitors
Interleukin-12/biosynthesis
Issue Date: 2011
Publisher: Wiley blackwell
Publisher version: http://dx.doi.org/10.1002/hep.23980
ISSN: 0270-9139
Citation: Diaz-Valdes N, Manterola L, Belsue V, Riezu-Boj JI, Larrea E, Echeverria I, et al. Improved dendritic cell-based immunization against hepatitis C virus using peptide inhibitors of interleukin 10. Hepatology 2011 Jan;53(1):23-31.
Abstract
The high levels of interleukin 10 (IL-10) present in chronic hepatitis C virus (HCV) infection have been suggested as responsible for the poor antiviral cellular immune responses found in these patients. To overcome the immunosuppressive effect of IL-10 on antigen-presenting cells such as dendritic cells (DCs), we developed peptide inhibitors of IL-10 to restore DC functions and concomitantly induce efficient antiviral immune responses. Two IL-10-binding peptides (p9 and p13) were selected using a phage-displayed library and their capacity to inhibit IL-10 was assessed in a bioassay and in STAT-3 (signal transducer and activator of transcription 3) phosphorylation experiments in vitro. In cultures of human leukocytes where HCV core protein induces the production of IL-10, p13 restored the ability of plasmacytoid DC to produce interferon alpha (IFN-α) after Toll-like receptor 9 (TLR9) stimulation. Similarly, when myeloid DCs were stimulated with CD40L in the presence of HCV core, p9 enhanced IL-12 production by inhibiting HCV core-induced as well as CD40L-induced IL-10. Moreover, in vitro, p13 potentiated the effect of maturation stimuli on human and murine DC, increasing their IL-12 production and stimulatory activity, which resulted in enhanced proliferation and IFN-γ production by responding T-cells. Finally, immunization with p13-treated murine DC induced stronger anti-HCV T-cell responses not only in wildtype mice but also in HCV transgenic mice and in mice transiently expressing HCV core in the liver. CONCLUSION: These results suggest that IL-10 inhibiting peptides may have important applications to enhance anti-HCV immune responses by restoring the immunostimulatory capabilities of DC.
Permanent link: http://hdl.handle.net/10171/20359
Appears in Collections:DA - CIMA - Terapia génica y Hepatología - Inmunología clínica - Artículos de revista
DA - CUN - Medicina interna - Artículos de revista
DA - CIMA - Terapia génica y Hepatología - Virología - Artículos de revista
DA - Medicina - Medicina Interna - Artículos de revista
DA - CIMA - Terapia génica y Hepatología - Inmunología experimental - Artículos de revista
DA - CIMA - Terapia génica y Hepatología - Inmunología hepatitis virales - Artículos de revista

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