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

Abstract

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.

• Authors: Mariko Yokouchi, Akiharu Kubo, Hiroshi Kawasaki, Kazue Yoshida, Ken Ishii, Mikio Furuse, Masayuki Amagai
• Journal: Journal of dermatological science (J Dermatol Sci) Vol. 77 Issue 1 Pg. 28-36 (Jan 2015) ISSN: 1873-569X [Electronic] Netherlands
• PMID: 25511077 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Filaggrin Proteins
• Haptens
• Intermediate Filament Proteins
• Biotin

Topics

• Animals
• Biotin (chemistry)
• Dermatitis, Atopic (immunology)
• Epidermis (immunology, metabolism)
• Female
• Filaggrin Proteins
• Gene Expression Regulation
• Haptens (chemistry)
• Inflammation (metabolism)
• Intermediate Filament Proteins (chemistry, genetics)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Microscopy, Fluorescence
• Permeability
• Skin (immunology)
• Tight Junctions (immunology)