Transcriptional regulation of dectin-2 promoter in transgenic mouse

Despite a preeminent role of epidermal Langerhans cells (LC) in inducing primary immunity, application of gene-based modification to LC function is limited by lack of well-defined transcription regulatory units that can direct LC-specific gene expression. Previously we reported that the promoter activity of a 5'-flanking region of the dectin-2 gene (Dec2FR) is highly targeted to epidermal LC of transgenic mice bearing a Dec2FR-driven Luc gene. Using the mice, in which transcription activity of Dec2FR is measured by Luc assays, presently we characterized regulation of Dec2FR activity in leukocyte subpopulations under resting and activation status. Luc activity was highly variable in LC isolated from different skin areas and detected in other DC subset (dermal DC) but the levels were much lower than in resting LC. Activation of leukocytes markedly up-regulated Luc activity in all four subpopulations (CD11c+ splenic DC, Mac-1high peritoneal macrophages, splenic B220+ B cells, and CD3+ T cells). However, these levels remained lower than those in the resting and activated LC. These findings indicate that dectin-2 promoter activity remains targeted to epidermal LC even after activation of leukocytes, suggesting a high potential of Dec2FR to engineer LC-targeted gene expression to heighten efficacy of genetic vaccination and to manipulate phenotypes of preexisting immunity (Th1 vs. Th2).