Aberrant serine protease activities in atopic dermatitis

Atopic dermatitis (AD) is a chronic inflammatory skin disease; the three major factors responsible for AD, i.e., epidermal barrier dysfunction, allergic inflammation, and itching, interact with each other to form a pathological condition. Excessive protease activities are characteristic abnormalities that affect the epi-dermal barrier in patients with AD. In normal skin, epidermal serine protease activities are controlled by kallikrein-related peptidases (KLKs) and their inhibitors, including lympho-epithelial Kazal-type-related inhibitor (LEKTI). In AD lesions, KLKs are excessively expressed, which results in the enhancement of epi-dermal serine protease activities and facilitates the invasion by allergens and microorganisms. In addition, some KLKs can activate protease-activated receptor 2 (PAR2) in epidermal keratinocytes and peripheral nerves, resulting in the induction of inflammation and itching. Furthermore, in AD patients with single nucleotide polymorphism (SNP) such as E420K and D386N of SPINK5 which encodes LEKTI, LEKTI function is attenuated, resulting in the activation of KLKs and easy invasion by allergens and microorganisms. Further analysis is needed to elucidate the detailed mechanism underlying the control of serine protease activities, which may lead to the development of new therapeutic and prophylactic agents for AD.(c) 2022 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.

© 2022 Japanese Society for Investigative Dermatology. This manuscript version is made available under the CC-BY-NC-ND 4.0 License. http://creativecommons.org/licenses/by-nc-nd/4.0/. This is the accepted manuscript version. The formal published version is available at [https://doi.org/10.1016/j.jdermsci.2022.06.004] .

This fulltext is available in July 2023.