Epidermal Langerhans cell-targeted gene expression by a dectin-2 promoter

M. Bonkobara, P. K. Zukas, S. Shikano, S. Nakamura, Ponciano D Cruz, Kiyoshi Ariizumi

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Despite their critical function as APCs for primary immune responses, dendritic cells (DC) and Langerhans cells (LC) have been rarely used as targets of gene-based manipulation because well-defined regulatory elements controlling LC/DC-specific expression have not been identified. Previously, we identified dectin-2, a C-type lectin receptor expressed selectively by LC-like XS cell lines and by LC within mouse epidermis. Because these characteristics raised the possibility that dectin-2 promoter may direct LC/DC-specific gene expression, we isolated a 3.2-kb nucleotide fragment from the 5′-flanking region of the dectin-2 gene (Dec2FR) and characterized its regulatory elements and the transcriptional activity using a luciferase (Luc) reporter system. The Dec2FR contains a putative TATA box and cis-acting elements, such as the IFN-stimulated response element, that drive gene expression specifically in XS cells. Dec2FR comprises repressor, enhancer, and promoter regions, and the latter two regions coregulate XS cell-specific gene expression. In transgenic mice bearing a Dec2FR-regulated Luc gene, the skin was the predominant site of Luc activity and LC were the exclusive source of such activity within epidermis. By contrast, other APCs (DC, macrophages, and B cells) and T cells expressed Luc activity close to background levels. We conclude that epidermal LC are targeted selectively for high-level constitutive gene expression by Dec2FR in vitro and in vivo. Our findings lay the foundation for use of the dectin-2 promoter in LC-targeted gene expression systems that may enhance vaccination efficacy and regulate immune responses.

Original languageEnglish (US)
Pages (from-to)6893-6900
Number of pages8
JournalJournal of Immunology
Volume167
Issue number12
StatePublished - Dec 15 2001

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Langerhans Cells
Gene Expression
Luciferases
Dendritic Cells
Epidermis
Transcriptional Regulatory Elements
Genes
C-Type Lectins
TATA Box
mouse dectin-2
5' Flanking Region
Response Elements
Genetic Promoter Regions
Transgenic Mice
Vaccination
B-Lymphocytes
Nucleotides
Macrophages
T-Lymphocytes
Cell Line

ASJC Scopus subject areas

  • Immunology

Cite this

Bonkobara, M., Zukas, P. K., Shikano, S., Nakamura, S., Cruz, P. D., & Ariizumi, K. (2001). Epidermal Langerhans cell-targeted gene expression by a dectin-2 promoter. Journal of Immunology, 167(12), 6893-6900.

Epidermal Langerhans cell-targeted gene expression by a dectin-2 promoter. / Bonkobara, M.; Zukas, P. K.; Shikano, S.; Nakamura, S.; Cruz, Ponciano D; Ariizumi, Kiyoshi.

In: Journal of Immunology, Vol. 167, No. 12, 15.12.2001, p. 6893-6900.

Research output: Contribution to journalArticle

Bonkobara, M, Zukas, PK, Shikano, S, Nakamura, S, Cruz, PD & Ariizumi, K 2001, 'Epidermal Langerhans cell-targeted gene expression by a dectin-2 promoter', Journal of Immunology, vol. 167, no. 12, pp. 6893-6900.
Bonkobara M, Zukas PK, Shikano S, Nakamura S, Cruz PD, Ariizumi K. Epidermal Langerhans cell-targeted gene expression by a dectin-2 promoter. Journal of Immunology. 2001 Dec 15;167(12):6893-6900.
Bonkobara, M. ; Zukas, P. K. ; Shikano, S. ; Nakamura, S. ; Cruz, Ponciano D ; Ariizumi, Kiyoshi. / Epidermal Langerhans cell-targeted gene expression by a dectin-2 promoter. In: Journal of Immunology. 2001 ; Vol. 167, No. 12. pp. 6893-6900.
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