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

Despite their critical function as APCs for primary immune responses, dendr itic cells (DC) and Langerhans cells (LC) have been rarely used as targets of gene-based manipulation because well-defined regulatory elements control ling LC/DC-specific expression have not been identified. Previously, we ide ntified dectin-2, a C-type lectin receptor expressed selectively by LC-like XS cell lines and by LC within mouse epidermis. Because these characterist ics 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'-flan king 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, s uch as the IFN-stimulated response element, that drive gene expression spec ifically in XS cells. Dec2FR comprises repressor, enhancer, and promoter re gions, and the latter two regions coregulate XS cell-specific gene expressi on. In transgenic mice bearing a Dec2FR-regulated Luc gene, the skin was th e 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 c onclude that epidermal LC are targeted selectively for high-level constitut ive gene expression by Dec2FR in vitro and in vivo. Our findings lay the fo undation for use of the dectin-2 promoter in LC-targeted gene expression sy stems that may enhance vaccination efficacy and regulate immune responses.