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

Interleukin-15 liver gene transfer increases the number and function of IKDCs and NK cells.
Authors: Arina, A. (Ainhoa)
Murillo, O. (Oihana)
Dubrot, J. (Juan)
Azpilicueta, A. (Arantza)
Gabari, I. (Izaskun)
Perez-Gracia, J.L. (José Luis)
Alfaro, C. (Carlos)
Berasain, C. (Carmen)
Prieto, J. (Jesús)
Ferrini, S. (S.)
Hervas-Stubbs, S. (Sandra)
Melero, I. (Ignacio)
Keywords: Interleukin-15
Gene transfer
Natural killer cells
Dendritic cells
Issue Date: 2008
Publisher: Nature Publishing Group
Publisher version: http://www.nature.com/gt/journal/v15/n7/full/gt20084a.html
ISSN: 1476-5462
Citation: Arina A, Murillo O, Dubrot J, Azpilikueta A, Gabari I, Perez-Gracia JL, et al. Interleukin-15 liver gene transfer increases the number and function of IKDCs and NK cells. Gene Ther 2008 Apr;15(7):473-483.
Abstract
The surface phenotype CD3-NK1.1+DX5+CD11c(int)B220+GR1- has been recently ascribed to a novel subset of mouse leukocytes termed interferon (IFN)-producing killer dendritic cells (IKDCs) that shares functions with natural killer (NK) cells and DCs. Interleukin-15 (IL-15) is critical for NK cells but its relationship with IKDC remained unexplored. An expression cassette encoding human IL-15 (hIL-15) has been transferred by hydrodynamic injection into the liver of mice, resulting in transient expression of the cytokine that is detectable during the first 48 h. hIL-15 hydrodynamic gene transfer resulted in an expansion of NK cells and IKDCs. Relative expansions of IKDCs were more dramatic in the IL-15 gene-transferred hepatic tissue than in the spleen. Adoptively transferred DX5+ cells comprising both NK cells and IKDCs proliferated in response to hydrodynamic injection of hIL-15, indicating that quantitative increases are at least in part the result of proliferation from already differentiated cells. Expansion is accompanied by enhanced cytolytic activity and increased expression of TRAIL and CD137 (4-1BB), without augmenting interferon-gamma production. The effects of a single hydrodynamic injection surpassed those of two intraperitoneal doses of the recombinant protein. The novel functional link between circulating IL-15 and IKDCs opens new possibilities to study the biology and applications of this minority cell subset.
Permanent link: http://hdl.handle.net/10171/20370
Appears in Collections:DA - CIMA - Terapia génica y Hepatología - Oncobiología - Artículos de revista
DA - Medicina - Medicina Interna - Artículos de revista
DA - CIMA - Terapia génica y Hepatología - Inmunología terapia génica - Artículos de revista

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