Chemerin is a chemoattractant ligand for chemokine like receptor 1 (CMKLR1). CMKLR1-positive human plasmacytoid dendritic cells and NK cells can be recruited to diseased skin in a chemerin-dependent manner. Chemerin is predicted to share similar tertiary structure with antibacterial cathelicidins, and recombinant chemerin has antimicrobial activity. Here we show that endogenous chemerin protein is abundant in human epidermis, and that inhibition of bacteria growth by exudates from organ cultures of primary human skin keratinocytes is largely chemerin-dependent. Using a panel of overlapping chemerin derived synthetic peptides, we demonstrate that the highly positively-charged chemerin domain Val66-Pro85 embodies the majority of the anti-microbial activity, which is comparable in potency to other antimicrobial proteins. Finally, we demonstrate that Val66-Pro85 likely functions by direct bacterial lysis. Therefore, chemerin may operate at multiple levels in skin defense, as a chemoattractant and an antimicrobial agent.
- Copyright © 2013 by The American Association of Immunologists, Inc.