Th17 micro-milieu regulates NLRP1-dependent caspase-5 activity in skin autoinflammation.
- Zwicker S Department of Dermatology and Allergology, Ludwig-Maximilian University Munich, Frauenlobstr. 9-11, Munich, Germany.
- Hattinger E Department of Dermatology and Allergology, Ludwig-Maximilian University Munich, Frauenlobstr. 9-11, Munich, Germany.
- Bureik D Department of Dermatology and Allergology, Ludwig-Maximilian University Munich, Frauenlobstr. 9-11, Munich, Germany.
- Batycka-Baran A Department of Dermatology and Allergology, Ludwig-Maximilian University Munich, Frauenlobstr. 9-11, Munich, Germany.
- Schmidt A Division of Clinical Pharmacology, Medizinische Klinik IV, Ludwig-Maximilian University Munich, Ziemssenstr. 1, Munich, Germany.
- Gerber PA Department of Dermatology, University Hospital Düsseldorf, Moorenstrasse 5, Düsseldorf, Germany.
- Rothenfusser S Division of Clinical Pharmacology, Medizinische Klinik IV, Ludwig-Maximilian University Munich, Ziemssenstr. 1, Munich, Germany.
- Gilliet M Department of Dermatology, University Hospital of Lausanne, CHUV University Hospital, Rue du Bugnon 46, Lausanne, Switzerland.
- Ruzicka T Department of Dermatology and Allergology, Ludwig-Maximilian University Munich, Frauenlobstr. 9-11, Munich, Germany.
- Wolf R Department of Dermatology and Allergology, Ludwig-Maximilian University Munich, Frauenlobstr. 9-11, Munich, Germany.
- 2017-04-20
Published in:
- PloS one. - 2017
Adaptor Proteins, Signal Transducing
Apoptosis Regulatory Proteins
Caspases
Cells, Cultured
DNA
Gene Expression Regulation
Humans
Inflammasomes
Interferon-gamma
Interleukin-17
Interleukin-1beta
Keratinocytes
Psoriasis
S100 Calcium Binding Protein A7
S100 Proteins
Signal Transduction
Skin
Th17 Cells
Transfection
Vitamin D
English
IL-1β is a potent player in cutaneous inflammation and central for the development of a Th17 micro-milieu in autoinflammatory diseases including psoriasis. Its production is controlled at the transcriptional level and by subsequent posttranslational processing via inflammatory caspases. In this study, we detected inflammatory caspase-5 active in epidermal keratinocytes and in psoriatic skin lesions. Further, interferon-γ and interleukin-17A synergistically induced caspase-5 expression in cultured keratinocytes, which was dependent on the antimicrobial peptide psoriasin (S100A7). However, diseases-relevant triggers for caspase-5 activity and IL-1β production remain unknown. Recently, extranuclear DNA has been identified as danger-signals abundant in the psoriatic epidermis. Here, we could demonstrate that cytosolic double-stranded (ds) DNA transfected into keratinocytes triggered the activation of caspase-5 and the release of IL-1β. Further, interleukin-17A promoted caspase-5 function via facilitation of the NLRP1-inflammasome. Anti-inflammatory vitamin D interfered with the IL-1β release and suppressed caspase-5 in keratinocytes and in psoriatic skin lesions. Our data link the disease-intrinsic danger signals psoriasin (S100A7) and dsDNA for NLPR1-dependent caspase-5 activity in psoriasis providing potential therapeutic targets in Th17-mediated skin autoinflammation.
- Language
-
- English
- Open access status
- gold
- Identifiers
-
- DOI 10.1371/journal.pone.0175153
- PMID 28422993
- Persistent URL
- https://sonar.ch/global/documents/20633
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