Association of Cathepsin E Deficiency with Development of Atopic Dermatitis

Takayuki Tsukuba, Kuniaki Okamoto, Yoshiko Okamoto, Michiyo Yanagawa, Keiko Kohmura, Yoshiyuki Yasuda, Hiroshi Uchi, Takeshi Nakahara, Masutaka Furue, Keiko Nakayama, Tomoko Kadowaki, Kenji Yamamoto, Keiichi I. Nakayama

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65 Citations (Scopus)

Abstract

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 pathogen-free 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.

Original languageEnglish
Pages (from-to)893-902
Number of pages10
JournalJournal of Biochemistry
Volume134
Issue number6
DOIs
Publication statusPublished - Dec 2003
Externally publishedYes

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Keywords

  • Aspartic proteinase
  • Atopic dermatitis
  • Cathepsin
  • Proteinase

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry
  • Molecular Biology

Cite this

Tsukuba, T., Okamoto, K., Okamoto, Y., Yanagawa, M., Kohmura, K., Yasuda, Y., Uchi, H., Nakahara, T., Furue, M., Nakayama, K., Kadowaki, T., Yamamoto, K., & Nakayama, K. I. (2003). Association of Cathepsin E Deficiency with Development of Atopic Dermatitis. Journal of Biochemistry, 134(6), 893-902. https://doi.org/10.1093/jb/mvg216