Development of a Langerhans cell-targeted gene therapy format using a dendritic cell-specific promoter

A. Morita, K. Ariizumi, R. Ritter, J. V. Jester, T. Kumamoto, S. A. Johnston, A. Takashima

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

Langerhans cells (LC), which are a skin-specific member of the dendritic cell (DC) family of antigen presenting cells, play critical roles in the initiation of cellular immune responses in the skin. We developed a LC-targeted gene therapy format in this study, aimed at the establishment of in situ protocols for genetic manipulation of LC function. Dectin-2 is a unique C-type lectin that is expressed selectively by DC, including epidermal LC. A 3.2 kb 5′ flanking fragment isolated from the mouse dectin-2 gene, termed the dectin-2 promoter (pDec2), exhibited significant transcriptional activities in epidermal-derived DC lines of the XS series, but not in any of the tested non-DC lines. When pDec2-driven luciferase gene (pDec2-Luc) or enhanced green fluorescence protein gene (pDec2-EGFP) was delivered to mouse skin using the gene gun, expression of the corresponding gene product was observed in the epidermal compartment almost exclusively by the IA+ population (ie LC). LC in the gene gun-treated sites showed features of mature DC and they migrated to the draining lymph node, suggesting that LC-targeted gene expression may lead to the development of immune responses. In fact, EGFP-specific cellular immune responses became detectable after gene gun-mediated delivery of pDec2-EGFP plasmid. These results introduce a new concept that LC function can be genetically manipulated in situ by the combination of gene gun-mediated DNA delivery and a DC-specific promoter.

Original languageEnglish (US)
Pages (from-to)1729-1737
Number of pages9
JournalGene Therapy
Volume8
Issue number22
DOIs
StatePublished - Dec 1 2001

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Keywords

  • Dectin-2 promoter
  • Dendritic cells
  • Gene gun
  • Langerhans cells
  • Transcriptional regulation

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

Cite this

Morita, A., Ariizumi, K., Ritter, R., Jester, J. V., Kumamoto, T., Johnston, S. A., & Takashima, A. (2001). Development of a Langerhans cell-targeted gene therapy format using a dendritic cell-specific promoter. Gene Therapy, 8(22), 1729-1737. https://doi.org/10.1038/sj.gt.3301580