Thymic stromal lymphopoietin links keratinocytes and dendritic cell–derived IL-23 in patients with psoriasis - 01/08/14
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Abstract |
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.
Le texte complet de cet article est disponible en PDF.Key words : Thymic stromal lymphopoietin, dendritic cells, IL-23, psoriasis, CD40 ligand, skin inflammation
Abbreviations used : AD, CD40L, DC, GAPDH, STAT, TBS, TSLP
Plan
The research leading to these results has received funding from the European Union's Seventh Framework Programme FP7/2007-2013 under grant agreement no. 261366, a European Community FP6 Marie Curie Excellence Grant (014162), Agence Nationale pour la Recherche (ANR), Fondation pour la Recherche Médicale (FRM), and the German Research Foundation FOR-729. |
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Disclosure of potential conflict of interest: A. Cavani has received payment from Novartis for delivering lectures. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 134 - N° 2
P. 373 - août 2014 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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