The Paneth cells (secretory epithelial cells) of the human small intestine protect against pathogenic microbial infection through the release of antibiotic polypeptides, such as defensins, but the precise identity of the mediators involved in this process remains unclear. In May 20 Nature Immunology, Dipankar Ghosh and colleagues from The Cleveland Clinic Foundation, Ohio, show that the trypsin of Paneth cells is the enzyme responsible for processing human defensin-5 (HD5), stored as a propeptide in the Paneth cells.

Gosh et al. examined samples of normal human ileal tissue derived from surgical resection and from endoscopically obtained biopsies. They found that a specific pattern of trypsin isozymes is expressed in Paneth cells and that trypsin colocalizes with HD. In addition, trypsin efficiently cleaves HD5 propeptides to forms identical to those isolated in vivo.

"By acting as a prodefensin convertase, and perhaps through signaling effects, trypsin released from Paneth...