Epidermal tight junction barrier function is altered by skin inflammation, but not by filaggrin-deficient stratum corneum

Mariko Yokouchi, Akiharu Kubo, Hiroshi Kawasaki, Kazue Yoshida, Ken Ishii, Mikio Furuse, Masayuki Amagai

研究成果: Article査読

54 被引用数 (Scopus)

抄録

Background: The tight junction (TJ) barrier is located in the granular layer of the epidermis. Filaggrin deficiency predisposes patients to atopic dermatitis (AD) by impairing stratum corneum (SC) barrier function. Altered TJ barrier function has been observed in the skin of patients with AD; however, it remains unclear whether TJ function is influenced by filaggrin deficiency directly or secondarily via skin inflammation. Objective: To investigate the in vivo effects of filaggrin deficiency and skin inflammation on epidermal TJ function. Methods: Morphological changes in the TJ were investigated in filaggrin knockout mice and mice with hapten-induced dermatitis using en face visualization of epidermal sheets, and functional changes in the TJ were assessed with an in vivo permeation assay using tracers of various sizes. Results: In filaggrin knockout mice, there was no apparent change in the honeycomb morphology of the TJ, TJ component mRNA expression, or TJ barrier function in neonates and adults, indicating that filaggrin-deficiency had no direct effects on the TJ. By contrast, in mice with hapten-induced dermatitis, the mRNA expression of TJ components was decreased markedly and the TJ barrier function was size-dependently impaired: the TJ leaked small tracers (<5. kDa), but not large tracers (>30. kDa). Conclusion: Filaggrin deficiency did not affect the epidermal TJ barrier directly, but once dermatitis occurred, the skin inflammation induced TJ dysfunction. Since TJ dysfunction induces the SC barrier impairment, skin inflammation will enhance skin permeability to external antigens and result in a vicious cycle of barrier dysfunction and skin inflammation.

本文言語English
ページ(範囲)28-36
ページ数9
ジャーナルJournal of Dermatological Science
77
1
DOI
出版ステータスPublished - 2015 1 1

ASJC Scopus subject areas

  • 生化学
  • 分子生物学
  • 皮膚病学

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