Keratinocytes Share Gene Expression Fingerprint with Epidermal Langerhans Cells via mRNA Transfer

Abstract Epithelia-resident dendritic cells' (DCs) immune functions are influenced by epithelial-derived cytokines. Here we identified to our knowledge a previously unreported communication form between tissue-resident DCs and niche cells that allows direct intracellular material exchange between the parties. We show that many keratinocytes (KC)-specific molecules such as keratins and adhesion molecules could be detected in the epidermal-resident Langerhans cells (LCs) as mRNA and protein. Furthermore, KC-derived Cre led to genetic recombination in the LCs. We also found that LCs containing KC-derived material were more prone to migration. The KC-specific signatures were transferred from KCs to LCs through an exosome-independent mechanism that likely involved nanotubes/dendrites. The transfer of material between epithelial cells and epithelia-associated DCs was not limited to mice or to KC-to-LC transfer. Taken together, these data suggest that the epithelial environment might have a long-term effect on DC biology and that genetic tools that specifically target epithelial cells also affect tissue-resident immune cells.