Influence of Th2 cytokines on the cornified envelope, tight junction proteins, and ß-defensins in filaggrin-deficient skin equivalents

Item Type:	Article
Title:	Influence of Th2 cytokines on the cornified envelope, tight junction proteins, and ß-defensins in filaggrin-deficient skin equivalents
Creators Name:	Hönzke, S. and Wallmeyer, L. and Ostrowski, A. and Radbruch, M. and Mundhenk, L. and Schäfer-Korting, M. and Hedtrich, S.
Abstract:	Atopic dermatitis is a chronic skin condition with complex etiology. It is characterized by skin barrier defects and T helper type 2 (Th2)-polarized inflammation. Although mutations in the filaggrin gene are known to be prominent genetic risk factors for the development of atopic dermatitis, the interdependency between these and an altered cytokine milieu is not fully understood. In this study, we evaluated the direct effects of filaggrin deficiency on the cornified envelope, tight junction proteins, and innate immune response, and report the effects of Th2 cytokines in normal and filaggrin-deficient skin equivalents. Supplementation with IL-4 and IL-13 led to distinct histologic changes and significantly increased skin surface pH, both of which were enhanced in filaggrin knockdown skin equivalents. We detected a compensatory up-regulation of involucrin and occludin in filaggrin-deficient skin that was dramatically disturbed when simultaneous inflammation occurred. Furthermore, we found that a lack of filaggrin triggered an up-regulation of human β-defensin 2 via an unknown mechanism, which was abolished by Th2 cytokine supplementation. Taken together, these results indicate that defects in the epidermal barrier, skin permeability, and cutaneous innate immune response are not primarily linked to filaggrin deficiency but are rather secondarily induced by Th2 inflammation.
Keywords:	Atopic Dermatitis, Cultured Cells, Cytokines, Epidermis, Filaggrin Proteins, Immunohistochemistry, Interleukin-13, Interleukin-4, Intermediate Filament Proteins, Needle Biopsy, Reference Values, Th2 Cells, Tight Junction Proteins, beta-Defensins
Source:	Journal of Investigative Dermatology
ISSN:	0022-202X
Publisher:	Elsevier
Volume:	136
Number:	3
Page Range:	631-639
Date:	March 2016
Official Publication:	https://doi.org/10.1016/j.jid.2015.11.007
PubMed:	View item in PubMed

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