Transgenic kallikrein 5 mice reproduce major cutaneous and systemic hallmarks of Netherton syndrome

Counterregulation between thymic stromal lymphopoietin– and IL-23–driven immune axes shapes skin inflammation in mice with epidermal barrier defects

“…Supporting this speculation, in an AD mouse model (flaky tail mice) dominant T H 2 and T H 17 features were reported at an early and later stage, respectively 12,14 ; in addition, both T H 2 and T H 17 features have been characterized recently in an NS mouse model. 16 We have identified S aureus colonization in skin of Cdsn iep2/2 mice, as universally occurs in human patients with PSS-B, NS, and AD. Our data showed that topical administration of antibiotics that eliminate skin bacteria, including S aureus, suppresses the IL-23/type 17 axis, which is in agreement with the role of S aureus in induction of the IL-23/type 17 inflammatory axis.…”

“…[5][6][7][8][9][10] In addition, studies in mouse models also reported varied inflammatory types in barrier-defective skin, which were interpreted as either type 2, 11-13 type 17, 14 or mixed type 2/17 inflammation. 15,16 These seemingly contradictory reports reflect the complexity and heterogeneity of the inflammation occurring in barrier-defective skin, which remain poorly understood. In view of this, a variety of biological treatments have been or are being developed for interventions of AD and AD-like diseases.…”

pH in nature, humans and skin

“…pH regulates the activity of the serine protease chymotryptic enzyme (kallikrein 7) involved in corneodesmosome disintegration and desquamation (Fig. ) . Alkalization of the skin induced kallikrein 5 and activates PAR‐2 resulting in thymic stromal lymphopoietin secretion, cutaneous T‐helper 2 response and finally eczematous reactions.…”

“…3). 83,84 Alkalization of the skin induced kallikrein 5 and activates PAR-2 resulting in thymic stromal lymphopoietin secretion, cutaneous T-helper 2 response and finally eczematous reactions. In contrast, weak acidification of eczematous skin in mice reduced kallikrein 5 activity and thus ameliorated dermatitis in this model.…”

Attenuated kallikrein‐related peptidase activity disrupts desquamation and leads to stratum corneum thickening in human skin equivalent models

“…To examine proteolytic activity, the epidermis of native skin and HSEs were isolated and finely minced in 1 mol L À1 acetic acid, as described by Furio et al 26 Following extraction at 4°C for 24-48 h, the samples were clarified by centrifugation at 13 000 g for 20 min before the supernatant was frozen at À80°C, freeze-dried and resuspended in distilled water. Protein content was determined using the bicinchoninic acid protein assay reagent (Pierce, Thermo Fisher Scientific, Rockford, IL, U.S.A.).…”