Thymic stromal lymphopoietin links keratinocytes and dendritic cell–derived IL-23 in patients with psoriasis - 01/08/14
, Lucia Pattarini, PhD a, c, d, ∗, Carolina Martinez-Cingolani, PhD a, c, d, Stephan Meller, MD e, Marie-Helene Donnadieu, MSc a, c, Sofia I. Bogiatzi, MD, PhD a, c, Maria I. Fernandez, PhD a, c, f, g, Maxime Touzot, MD, PhD a, c, Jean-Christophe Bichet, MD h, Fabien Reyal, MD, PhD i, Maria Paola Paronetto, PhD j, Andrea Chiricozzi, MD k, l, Sergio Chimenti, MD k, Francesca Nasorri, PhD m, Andrea Cavani, MD, PhD m, Andreas Kislat, MSc e, Bernhard Homey, MD, PhD e, Vassili Soumelis, MD, PhD a, c, d, ⁎ 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 numéro
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