Association of Cathepsin E Deficiency with Development of Atopic Dermatitis

  • Tsukuba Takayuki
    Department of Pharmacology Graduate School of Dental Science, Kyushu University
  • Okamoto Kuniaki
    Department of Pharmacology Graduate School of Dental Science, Kyushu University
  • Okamoto Yoshiko
    Department of Biochemistry, Daiichi University College of Pharmaceutical Sciences
  • Yanagawa Michiyo
    Department of Pharmacology Graduate School of Dental Science, Kyushu University
  • Kohmura Keiko
    Department of Pharmacology Graduate School of Dental Science, Kyushu University
  • Yasuda Yoshiyuki
    Department of Pharmacology Graduate School of Dental Science, Kyushu University
  • Uchi Hiroshi
    Department of Dermatology, Graduate School of Medical Science, Kyushu University
  • Nakahara Takeshi
    Department of Dermatology, Graduate School of Medical Science, Kyushu University
  • Furue Masutaka
    Department of Dermatology, Graduate School of Medical Science, Kyushu University
  • Nakayama Keiko
    Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University
  • Kadowaki Tomoko
    Department of Pharmacology Graduate School of Dental Science, Kyushu University
  • Yamamoto Kenji
    Department of Pharmacology Graduate School of Dental Science, Kyushu University
  • Nakayama Keiichi I.
    Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University

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Description

Atopic dermatitis (AD) is a pruritic inflammatory skin diseases associated with a family history of atropy. Here we show that mice lacking the endolysosomal aspartic proteinase cathepsin E spontaneously develop skin lesions similar to those of humans with AD when reared under conventional conditions but not under specific pathogenfree conditions. These mice showed the increase in the ratio of CD4+/CD8+ T cells, the strong polarization of naÏve T cells to T helper 2 cells, and the systemic accumulation of IL-18 and IL-1β accompanied by a marked increase in IL-4, IL-5, and IgE. The relative rates of degradation of IL-18 and IL-1β were significantly lower in cathepsin E-deficient mice than wild-type mice. These results strongly suggest that the development of AD in cathepsin E-deficient mice is initiated by systemic accumulation of IL-18 and IL-1β, mainly due to their reduced turnover rates. In addition, the reduced expression of cathepsin E was also observed in erythrocytes of both humans with AD and the AD mouse model NC/Nga. Cathepsin E deficiency might thus be responsible for the induction of AD in humans and mice.

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