Aberrant serine protease activities in atopic dermatitis

  • Shin Morizane
    Correspondence to: Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2–5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan.
    Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Japan
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  • Ko Sunagawa
    Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Japan
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  • Hayato Nomura
    Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Japan
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  • Mamoru Ouchida
    Department of Molecular Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Japan
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      • Trypsin- and chymotrypsin-like serine protease activities are enhanced in AD lesions.
      • Many KLKs expression is upregulated in AD lesions.
      • LEKTI function is decreased in some AD patients with SNPs E420K and D386N of SPINK5.
      • Aberrant serine protease activities disrupt the normal epidermal barrier function.
      • Some KLKs can activate PAR2 in epidermal keratinocytes and peripheral nerves


      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 epidermal 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 epidermal 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.


      AD (Atopic dermatitis), KLKs (kallikrein-related peptidases), LEKTI (lymphoepithelial Kazal-type-related inhibitor), PAR2 (protease-activated receptor 2), NS (Netherton syndrome)


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      Dr. Shin Morizane is a Professor & Chairman of Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Japan. He obtained his M.D. and Ph.D. in 2000 and 2006, respectively. He studied as a postdoctoral fellow at Division of Dermatology, University of California, San Diego, in the United States (Prof. Richard Gallo) from 2007 to 2009. His research interests include epidermal serine protease activities and innate immunity in the skin.