Kallikrein 14 activates the chemoattractant protein chemerin in human skin

Chemerin is a multifunctional protein that requires limited carboxyl-terminal proteolysis to manifest its chemotactic, antimicrobial, and metabolic activities. The role of chemerin in the maintenance of skin homeostasis has recently been demonstrated. The main enzymes responsible for processing chemerin in the skin, however, remain elusive. Due to their abundance in the skin and epidermis in particular, kallikreins (KLKs) are promising candidates. Here, using recombinant inactive chemerin, several isolated KLKs, and human primary keratinocytes gene-edited to silence KLK14, we demonstrate that KLK14 is a chemerin-processing enzyme in the skin, rapidly and stably activating this chemoattractant by generating the chemerin 156F and 158S isoforms.