Expansion of Foxp3-expressing regulatory T cells in vitro by dendritic cells modified with polymeric particles carrying a plasmid encoding interleukin-10.
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 TGFbeta 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.
Jia
Liang
L
Division of Pharmaceutical Sciences, Duquesne University, PA 15282, USA.
Kovacs
Jeffrey R
JR
Zheng
Ying
Y
Shen
Hongmei
H
Gawalt
Ellen S
ES
Meng
Wilson S
WS
D000818:Animals; D001483:Base Sequence; D001672:Biocompatible Materials; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism*; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors; D066298:In Vitro Techniques; D016753:Interleukin-10 / Q000235:genetics*; D019344:Lactic Acid; D007959:Lymphocyte Culture Test, Mixed; D008422:Materials Testing; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010316:Particle Size; D010957:Plasmids / Q000235:genetics*; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D011994:Recombinant Proteins / Q000235:genetics; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D015854:Up-Regulation
D001672:Biocompatible Materials; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D011108:Polymers; D011994:Recombinant Proteins; D016753:Interleukin-10; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid