Influence of Th2 Cytokines on the Cornified Envelope, Tight Junction Proteins, and β-Defensins in Filaggrin-Deficient Skin Equivalents
| Autor: | Moritz Radbruch, Stefan Hönzke, Sarah Hedtrich, Leonie Wallmeyer, Monika Schäfer-Korting, Anja Ostrowski, Lars Mundhenk |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
beta-Defensins Dermatology Biology Filaggrin Proteins Occludin Biochemistry Dermatitis Atopic Cornified envelope 030207 dermatology & venereal diseases 03 medical and health sciences 0302 clinical medicine Th2 Cells Intermediate Filament Proteins Reference Values medicine Humans skin and connective tissue diseases Involucrin Molecular Biology Cells Cultured Innate immune system Interleukin-13 Tight Junction Proteins integumentary system Biopsy Needle Atopic dermatitis Cell Biology medicine.disease Immunohistochemistry 030104 developmental biology Beta defensin Interleukin 13 Immunology Cytokines Interleukin-4 Epidermis Filaggrin |
| Zdroj: | Journal of Investigative Dermatology. 136(3):631-639 |
| ISSN: | 0022-202X |
| DOI: | 10.1016/j.jid.2015.11.007 |
| Popis: | 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 ?-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. |
| Databáze: | OpenAIRE |
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