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IL-29 is produced by T(H)17 cells and mediates the cutaneous antiviral competence in psoriasis
Kerstin Wolk1, Katrin Witte, Ellen Witte
1Interdisciplinary Group of Molecular Immunopathology, Dermatology/Medical Immunology, University Hospital Charité, 10117 Berlin, Germany.
Abstract:
Psoriasis and atopic dermatitis (AD) are the most common chronic inflammatory skin diseases. Although both patient groups show strongly impaired skin barrier function, only AD patients frequently suffer from cutaneous viral infections. The mechanisms underlying the distinct susceptibilities to these pathogenetic and often life-threatening infections are unknown. We show that antiviral proteins (AVPs) such as MX1, BST2, ISG15, and OAS2 were strongly elevated in psoriatic compared to AD lesions and healthy skin. Of 30 individually quantified cytokines in psoriatic lesions, interleukin-29 (IL-29) was the only mediator whose expression correlated with the AVP levels. IL-29 was absent in AD lesions, and neutralization of IL-29 in psoriatic skin reduced AVP expression. Accordingly, IL-29 raised AVP levels in isolated keratinocytes, epidermis models, and human skin explants, but did not influence antibacterial protein production. AVP induction correlated with increased antiviral defense of IL-29-treated keratinocytes. Furthermore, IL-29 elevated the expression of signaling elements, resulting in increased sensitivity of keratinocytes toward its own action. We identified T helper 17 (T(H)17) cells as IL-29 producers and demonstrated their ability to increase the antiviral competence of keratinocytes in an IL-29-dependent manner. Transforming growth factor-β and the activity of RORγt/RORα were most critical for the development of IL-29-producing T(H)17 cells. IL-29 secretion by these cells was dependent on NFAT and c-Jun N-terminal kinase and was inhibited by IL-4. These data suggest that T(H)17 cell-derived IL-29, which is absent in AD, mediates the robust antiviral state on psoriatic skin, and demonstrate a new function of T(H)17 cells.
Insights
Psoriasis patients have higher antiviral protein levels than atopic dermatitis (AD) patients due to interleukin-29 (IL-29) produced by T helper 17 (T(H)17) cells, enhancing skin
Area of Science:
- Immunology
- Dermatology
- Molecular Biology
Background:
- Psoriasis and atopic dermatitis (AD) are common inflammatory skin diseases with impaired skin barrier function.
- AD patients exhibit higher susceptibility to cutaneous viral infections compared to psoriasis patients, despite similar barrier defects.
- The underlying mechanisms for differential viral infection susceptibility remain unclear.
Purpose of the Study:
- To investigate the mechanisms behind the distinct susceptibility to viral infections in psoriasis versus AD.
- To identify key molecular mediators responsible for antiviral defense in psoriatic skin.
Main Methods:
- Quantitative analysis of antiviral proteins (AVPs) and cytokines in skin lesions.
- In vitro studies using keratinocytes, epidermis models, and skin explants.
- Identification of immune cell populations involved in cytokine production.
- Molecular pathway analysis of T helper 17 (T(H)17) cell differentiation and function.
Main Results:
- Antiviral proteins (AVPs) were significantly elevated in psoriatic lesions compared to AD lesions and healthy skin.
- Interleukin-29 (IL-29) expression strongly correlated with AVP levels in psoriasis and was absent in AD.
- IL-29 treatment increased AVP expression and enhanced keratinocyte antiviral defense, but not antibacterial defense.
- T(H)17 cells were identified as the primary source of IL-29, mediating keratinocyte antiviral competence in an IL-29-dependent manner.
- T(H)17 cell differentiation into IL-29 producers was regulated by TGF-β, RORγt/RORα, NFAT, and c-Jun N-terminal kinase, and inhibited by IL-4.
Conclusions:
- T(H)17 cell-derived IL-29 is crucial for establishing a robust antiviral state in psoriatic skin.
- The absence of IL-29 in atopic dermatitis contributes to its increased susceptibility to viral infections.
- This study reveals a novel role for T(H)17 cells in skin antiviral immunity.
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