期刊
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
卷 134, 期 2, 页码 373-+出版社
MOSBY-ELSEVIER
DOI: 10.1016/j.jaci.2014.04.022
关键词
Thymic stromal lymphopoietin; dendritic cells; IL-23; psoriasis; CD40 ligand; skin inflammation
资金
- European Union [261366]
- European Community [014162]
- Agence Nationale pour la Recherche (ANR)
- Fondation pour la Recherche Medicale (FRM)
- German Research Foundation [FOR-729]
Background: Thymic stromal lymphopoietin (TSLP) is a major proallergic cytokine that promotes T(H)2 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.
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