Thymic stromal lymphopoietin links keratinocytes and dendritic cell-derived IL-23 in patients with psoriasis.
J Allergy Clin Immunol
; 134(2): 373-81, 2014 Aug.
Article
in En
| MEDLINE
| ID: mdl-24910175
BACKGROUND: Thymic stromal lymphopoietin (TSLP) is a major proallergic cytokine that promotes TH2 responses through dendritic cell (DC) activation. Whether it also plays a role in human autoimmune inflammation and associated pathways is not known. OBJECTIVE: In this study we investigated the potential role of several epithelium-derived factors, including TSLP, in inducing IL-23 production by human DCs. We further dissected the role of TSLP in patients with psoriasis, an IL-23-associated skin autoimmune disease. METHODS: The study was performed in human subjects using primary cells and tissue samples from patients with psoriasis and healthy donors. We analyzed the production of IL-23 in vitro by blood and skin DCs. We studied the function for TSLP and its interaction with other components of the inflammatory microenvironment in situ and ex vivo. RESULTS: We found that TSLP synergized with CD40 ligand to promote DC activation and pathogenic IL-23 production by primary blood and skin DCs. In situ TSLP was strongly expressed by keratinocytes of untreated psoriatic lesions but not in normal skin. Moreover, we could demonstrate that IL-4, an important component of the TH2 inflammation seen in patients with atopic dermatitis, inhibited IL-23 production induced by TSLP and CD40 ligand in a signal transducer and activator of transcription 6-independent manner. CONCLUSION: Our results identify TSLP as a novel player within the complex psoriasis cytokine network. Blocking TSLP in patients with psoriasis might contribute to decreasing DC activation and shutting down the production of pathogenic IL-23.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Psoriasis
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Skin
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Dendritic Cells
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Keratinocytes
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Cytokines
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Interleukin-23
Type of study:
Prognostic_studies
Limits:
Adult
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Humans
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Male
/
Middle aged
Language:
En
Journal:
J Allergy Clin Immunol
Year:
2014
Document type:
Article
Country of publication:
United States