Modular expression analysis reveals functional conservation between human Langerhans Cells and mouse cross-priming dendritic cells

Characterization of functionally distinct Dendritic Cell (DC) subsets in mice has fueled interest in whether analogous counterparts exist in humans. Transcriptional modules of coordinately expressed genes were utilized for defining shared functions between the species. Comparing modules derived for four human skin DC subsets, and modules derived from the Immunological Genome Project database for all mouse DC subsets, revealed that human Langerhans Cells (LCs) and the mouse XCR1+CD8α+CD103+ DCs shared the Class I-mediated antigen processing and cross-presentation transcriptional modules that, however, were not seen in mouse LCs. Furthermore, human LCs were enriched in a transcriptional signature specific to the blood cross-presenting CD141/BDCA-3+ DCs, the proposed equivalent to mouse CD8α+ DCs. Consistent with our analysis, LCs were highly adept at inducing primary CTL responses. Thus, our study suggests that the function of LCs may not be conserved between mouse and human and supports human LCs as an especially relevant therapeutic target. RNA from sorted populations was purified using TRIzol. RNA was processed, amplified, labeled and hybridized at Washington University Core Facility (GTAC) with Illumina HumanHT-12 v4 Expression BeadChip. Data were background subtracted and quantile normalized.