The physiological role of DC-SIGN: A tale of mice and men

The innate immune receptor DC-SIGN (dendritic cell-specific intercellular adhesion molecule-3 grabbing nonintegrin) was discovered over a decade ago and was initially identified as a pattern recognition receptor. In addition to its ability to recognize a broad range of pathogen-derived ligands and self-glycoproteins, DC-SIGN also mediates intercellular adhesion, as well as antigen uptake and signaling, which is a functional hallmark of dendritic cells (DCs). Most research on DC-SIGN has relied on in vitro studies. The in vivo function of DC-SIGN is difficult to address, in part because there are eight genetic homologs in mice with no clear DC-SIGN ortholog. Here, we summarize the functions attributed to DC-SIGN based on in vitro data and discuss the limitations of available mouse models to uncover the physiological role of this receptor in vivo.