LEKTI-1 in sickness and in health

The stratum corneum (SC) is a biosensor that mediates responses to a variety of exogenous insults through various signalling mechanisms, including the activation of SC serine proteases (SP) kallikrein cascade. The SPINK5 gene encodes an SP inhibitor, the lympho-epithelial-Kazal-type-1 inhibitor (LEKTI-1), which in turn will buffer the excess of SP cascade initiation, key in the maintenance of permeability barrier homeostasis. We demonstrate that LEKTI processing can occur within the SC after secretion from stratum granulosum keratinocytes at least partially by klk7, an SC-specific chymotryptic SP. Unlike the recently described LEKTI-2, neither recombinant full-length LEKTI-1 nor recombinant LEKTI-1 fragments exhibit antimicrobial activity. Finally, we discuss the pathophysiological implications of LEKTI-1 in skin biology as well as its contribution to the pathogenesis of Netherton Syndrome and its potential involvement in atopic dermatitis.