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A peptide inhibitor of FOXP3 impairs regulatory T cell Activity and improves vaccine efficacy in mice
Authors: Casares, N. (Noelia)
Rudilla, F. (Francesc)
Arribillaga, L. (Laura)
Llopiz, D. (Diana)
Riezu-Boj, J.I. (José Ignacio)
Lozano, T. (Teresa)
Lopez-Sagaseta, J. (Jacinto)
Guembe, L. (L.)
Sarobe, P. (Pablo)
Prieto, J. (Jesús)
Borras-Cuesta, F. (Francisco)
Lasarte, J.J. (Juan José)
Keywords: Peptide
Inhibitor
FOXP3
T Cell Activity
Improves
Vaccine
Efficacy in mice
Issue Date: 25-Nov-2010
Publisher: American Association of Immunologists
Publisher version: http://dx.doi.org/10.4049/jimmunol.1001114
ISSN: 0022-1767
Citation: Casares N, Rudilla F, Arribillaga L, Llopiz D, Riezu-Boj JI, Lozano T, et al. A peptide inhibitor of FOXP3 impairs regulatory T cell activity and improves vaccine efficacy in mice. J Immunol 2010 Nov 1;185(9):5150-5159.
Abstract
Immunosuppressive activity of regulatory T cells (Treg) may contribute to the progression of cancer or infectious diseases by preventing the induction of specific immune responses. Using a phage-displayed random peptide library, we identified a 15-mer synthetic peptide, P60, able to bind to forkhead/winged helix transcription factor 3 (FOXP3), a factor required for development and function of Treg. P60 enters the cells, inhibits FOXP3 nuclear translocation, and reduces its ability to suppress the transcription factors NF-κB and NFAT. In vitro, P60 inhibited murine and human-derived Treg and improved effector T cell stimulation. P60 administration to newborn mice induced a lymphoproliferative autoimmune syndrome resembling the reported pathology in scurfy mice lacking functional Foxp3. However, P60 did not cause toxic effects in adult mice and, when given to BALB/c mice immunized with the cytotoxic T cell epitope AH1 from CT26 tumor cells, it induced protection against tumor implantation. Similarly, P60 improved the antiviral efficacy of a recombinant adenovirus expressing NS3 protein from hepatitis C virus. Functional inhibition of Treg by the FOXP3-inhibitory peptide P60 constitutes a strategy to enhance antitumor and antiviral immunotherapies.
Permanent link: http://hdl.handle.net/10171/14321
Appears in Collections: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
DA - Ciencias - HAP - Artículos de revista

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