期刊
BIOMATERIALS
卷 29, 期 9, 页码 1250-1261出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2007.11.015
关键词
non-viral gene delivery; interleukin-10; dendritic cells; regulatory T cells; Foxp3; PLGA
An emerging focus in experimental gene therapy is to employ non-viral vectors to deliver immunosuppressive cytokines aimed at attenuating damaging immune responses toward auto and alloantigens. In the current study, we present data showing that poly(lactic-co-glycolic acid) (PLGA) particles modified with the cationic peptide O10H6 (PLGA(O10H6)) were effective in delivering a mouse IL-10 encoding plasmid (pIL10) to skew bone marrow-derived dendritic cells (DCs) to downregulate T cell responses. T cells stimulated by the IL-10 gene-modified DCs exhibited characteristics of regulatory T (Treg) cells, as evident by upregulation of Foxp3 transcription factor concomitant with an increase in TGF beta production. Thus PLGA(O10H6) complexed with pIL10 delivers an overriding suppressive signal to T cells. Physical characterization of PLGA(O10H6) complexed with pIL10 revealed a stable colloidal dispersion. DNA molecules carried by PLGA(O10H6) were protected from serum digestion. Collectively, the results raise the prospects of using PLGA(O10H6) as a vector for delivering anti-inflammatory cytokine genes to modulate T cell responses in vivo. (C) 2007 Elsevier Ltd. All rights reserved.
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