title: Netherton syndrome: defective kallikrein inhibition in the skin leads to skin inflammation and allergy.
abstract: Netherton syndrome (NS) is an orphan genetic skin disease with a profound skin barrier defect and severe allergic manifestations. NS is caused by loss of function mutations in SPINK5 encoding lympho-epithelial Kazal-type inhibitor (LEKTI), a secreted multi-domain serine protease inhibitor expressed in stratified epithelia. Studies in mouse models and in NS patients have established that unopposed kallikrein 5 activity triggers stratum corneum detachment and activates PAR-2 signaling, leading to the autonomous production of pro-allergic and pro-inflammatory mediators. This emerging knowledge on NS pathogenesis has highlighted a central role for protease regulation in skin homeostasis but also in the complexity of the disease, and holds the promise of new specific treatments.
authors.forename: Laetitia
authors.initials: L
authors.lastname: Furio
authors.forename: Alain
authors.initials: A
authors.lastname: Hovnanian
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D006967:Hypersensitivity / Q000201:enzymology* / Q000473:pathology; D007249:Inflammation / Q000201:enzymology* / Q000473:pathology; D007610:Kallikreins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D056770:Netherton Syndrome / Q000201:enzymology* / Q000473:pathology* / Q000628:therapy; D012867:Skin / Q000473:pathology*
chemical_list: D007610:Kallikreins