Epidermal tight junction barrier function is altered by skin inflammation, but not by filaggrin-deficient stratum corneum. Issue 1 (January 2015)

• Record Type: Journal Article
• Authors: Yokouchi, Mariko; Kubo, Akiharu; Kawasaki, Hiroshi; Yoshida, Kazue; Ishii, Ken; Furuse, Mikio; Amagai, Masayuki
• Is Part Of: Journal of dermatological science. Volume 77:Issue 1(2015:Jan.)
• Page Start: 28
• Page End: 36
• Publication Date: 2015-01
• Subjects: Dermatology -- Periodicals; Skin Diseases -- Periodicals; Dermatologie -- Périodiques; 616.5005
• DOI: 10.1016/j.jdermsci.2014.11.007
• Languages: English
• ISSNs: 0923-1811

Abstract

<abstract abstract-type="author" id="abs0005"> <title id="sect0005">Abstract</title> <sec> <title id="sect0010">Background</title> <p id="spar0005">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.</p> </sec> <sec> <title id="sect0015">Objective</title> <p id="spar0010">To investigate the <italic>in vivo</italic> effects of filaggrin deficiency and skin inflammation on epidermal TJ function.</p> </sec> <sec> <title id="sect0020">Methods</title> <p id="spar0015">Morphological changes in the TJ were investigated in filaggrin knockout mice and mice with hapten-induced dermatitis using <italic>en face</italic> visualization of epidermal sheets, and functional changes in the TJ were assessed with an <italic>in vivo</italic> permeation assay using tracers of various sizes.</p> </sec> <sec> <title id="sect0025">Results</title> <p id="spar0020">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).</p> </sec> <sec> <title id="sect0030">Conclusion</title> <p id="spar0025">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.</p> </sec> </abstract>