Thymic stromal lymphopoietin links keratinocytes and dendritic cell–derived IL-23 in patients with psoriasis

• Published in: Journal of allergy and clinical immunology Vol. 134; no. 2; pp. 373 - 381.e4
• Main Authors: Volpe, Elisabetta, Pattarini, Lucia, Martinez-Cingolani, Carolina, Meller, Stephan, Donnadieu, Marie-Helene, Bogiatzi, Sofia I., Fernandez, Maria I., Touzot, Maxime, Bichet, Jean-Christophe, Reyal, Fabien, Paronetto, Maria Paola, Chiricozzi, Andrea, Chimenti, Sergio, Nasorri, Francesca, Cavani, Andrea, Kislat, Andreas, Homey, Bernhard, Soumelis, Vassili
• Format: Journal Article
• Language: English
• Published: United States Mosby, Inc 01.08.2014; Elsevier Limited
• Subjects: Adult; Allergy and Immunology; Biopsy; Blood banks; CD40 ligand; CD40 Ligand - genetics; CD40 Ligand - immunology; Colleges & universities; Cytokines - genetics; Cytokines - immunology; dendritic cells; Dendritic Cells - immunology; Dendritic Cells - pathology; Dermatitis, Atopic - genetics; Dermatitis, Atopic - immunology; Dermatitis, Atopic - pathology; Experiments; Gene Expression Regulation; Humans; IL-23; Immune system; Interleukin-23 - genetics; Interleukin-23 - immunology; Interleukin-4 - genetics; Interleukin-4 - immunology; Keratinocytes - immunology; Keratinocytes - pathology; Lymphocytes; Male; Middle Aged; Primary Cell Culture; Psoriasis; Psoriasis - genetics; Psoriasis - immunology; Psoriasis - pathology; Signal Transduction; Skin - immunology; Skin - pathology; skin inflammation; STAT6 Transcription Factor - genetics; STAT6 Transcription Factor - immunology; Th2 Cells - immunology; Th2 Cells - pathology; Thymic Stromal Lymphopoietin; Italy; CD40L; AD; TBS; TSLP; IL-23; STAT; Thymic stromal lymphopoietin; dendritic cells; psoriasis; CD40 ligand; GAPDH; skin inflammation; DC; Dendritic cell; Signal transducer and activator of transcription; Tris-buffered saline; Atopic dermatitis; Glyceraldehyde-3-phosphate dehydrogenase
• ISSN: 0091-6749; 1097-6825; 1097-6825
• DOI: 10.1016/j.jaci.2014.04.022

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. 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. 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. 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. 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.