HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bonkobara, M. Articles by Ariizumi, K. Search for Related Content PubMed PubMed Citation Articles by Bonkobara, M. Articles by Ariizumi, K.

Epidermal Langerhans Cell-Targeted Gene Expression by a Dectin-2 Promoter¹

Makoto Bonkobara^*, Paul K. Zukas^*, Sojin Shikano^*, Shinichiro Nakamura, Ponciano D. Cruz, Jr.^* and Kiyoshi Ariizumi^2,*

^* Department of Dermatology, University of Texas Southwestern Medical Center and Dallas Veterans Affairs Medical Center, Dallas, TX 75390; and Department of Veterinary Pathology, Nippon Veterinary and Animal Science University, Tokyo, Japan

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.

This article has been cited by other articles:

				L. Lopes, M. Dewannieux, U. Gileadi, R. Bailey, Y. Ikeda, C. Whittaker, M. P. Collin, V. Cerundolo, M. Tomihari, K. Ariizumi, et al. Immunization with a Lentivector That Targets Tumor Antigen Expression to Dendritic Cells Induces Potent CD8+ and CD4+ T-Cell Responses J. Virol., January 1, 2008; 82(1): 86 - 95. [Abstract] [Full Text] [PDF]

				Y. Aragane, A. Maeda, A. Schwarz, T. Tezuka, K. Ariizumi, and T. Schwarz Involvement of Dectin-2 in Ultraviolet Radiation-Induced Tolerance J. Immunol., October 1, 2003; 171(7): 3801 - 3807. [Abstract] [Full Text] [PDF]

				M. Bros, X.-L. Ross, A. Pautz, A. B. Reske-Kunz, and R. Ross The Human Fascin Gene Promoter Is Highly Active in Mature Dendritic Cells Due to a Stage-Specific Enhancer J. Immunol., August 15, 2003; 171(4): 1825 - 1834. [Abstract] [Full Text] [PDF]