Keratinocyte Expression of A20/TNFAIP3 Controls Skin Inflammation Associated with Atopic Dermatitis and Psoriasis
| Autor: | Denis A. Mogilenko, Delphine Staumont-Sallé, Geert van Loo, Wim Declercq, Peter Vandenabeele, Michael Devos, David Dombrowicz, Peter Tougaard, C. Becquart, Claus Bachert, Sandrine Quemener, Bart Staels, Barbara Gilbert, Hélène Dehondt, Sébastien Fleury |
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| Rok vydání: | 2019 |
| Předmět: |
Keratinocytes
0301 basic medicine Chemokine Biopsy Inflammation Dermatology Systemic inflammation Biochemistry Dermatitis Atopic Proinflammatory cytokine Mice 03 medical and health sciences 0302 clinical medicine Psoriasis medicine Animals Humans Molecular Biology Tumor Necrosis Factor alpha-Induced Protein 3 Mice Knockout integumentary system biology Reverse Transcriptase Polymerase Chain Reaction Tumor Necrosis Factor-alpha business.industry Cell Biology Atopic dermatitis medicine.disease 030104 developmental biology medicine.anatomical_structure Gene Expression Regulation 030220 oncology & carcinogenesis Immunology biology.protein Cytokines RNA Tumor necrosis factor alpha Epidermis medicine.symptom business Keratinocyte Signal Transduction |
| Zdroj: | Journal of Investigative Dermatology. 139:135-145 |
| ISSN: | 0022-202X |
| DOI: | 10.1016/j.jid.2018.06.191 |
| Popis: | Keratinocytes are key players in chronic inflammatory skin diseases. A20 regulates NF-κB-dependent expression of proinflammatory genes and cell death, but the impact of its expression in keratinocytes on systemic inflammation and skin disorders has not been determined. Comparative transcriptomic analysis of microdissected epidermis showed that A20 is down-regulated in involved epidermis, but not in dermis, of psoriasis and atopic dermatitis patients, suggesting that loss of A20 expression in keratinocytes increases the vulnerability for psoriasis/atopic dermatitis induction. We have previously shown that epidermis-specific A20 knockout mice (A20EKO) develop mild epidermal hyperplasia but no macroscopic skin inflammation. We now show that various cytokines and chemokines are up-regulated in A20EKO mouse skin. A20EKO mice also display systemic proinflammatory changes, even in the absence of skin immune cell infiltration, and an exacerbated disease severity upon induction of experimental psoriasis, atopic dermatitis, or skin barrier disruption. Keratinocytes showed increased proinflammatory gene expression in the absence of A20 in unstimulated and IL-17A-stimulated conditions, in part resulting from uncontrolled MyD88-dependent signaling. Our findings indicate that absence of A20 in keratinocytes leads to systemic inflammation at homeostatic conditions and is sufficient to exacerbate inflammatory skin disorders associated with different immune profiles by increasing cytokine and chemokine expression. |
| Databáze: | OpenAIRE |
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