Cutting Edge: Proinflammatory and Th2 Cytokines Synergize to Induce Thymic Stromal Lymphopoietin Production by Human Skin Keratinocytes

• Published in: Journal of Immunology Vol. 178; no. 6; pp. 3373 - 3377
• Main Authors: Bogiatzi, Sofia I, Fernandez, Isabel, Bichet, Jean-Christophe, Marloie-Provost, Marie-Annick, Volpe, Elisabetta, Sastre, Xavier, Soumelis, Vassili
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 15.03.2007
• Subjects: Adult; Aged; CD11c Antigen - immunology; Cells, Cultured; Cytokines - agonists; Cytokines - biosynthesis; Cytokines - immunology; Dendritic Cells - immunology; Female; Humans; Hypersensitivity - immunology; Hypersensitivity - metabolism; Hypersensitivity - therapy; Inflammation Mediators - agonists; Inflammation Mediators - immunology; Keratinocytes - immunology; Keratinocytes - metabolism; Middle Aged; Signal Transduction - immunology; Skin - immunology; Skin - metabolism
• ISSN: 0022-1767; 1550-6606; 1365-2567
• DOI: 10.4049/jimmunol.178.6.3373

Thymic stromal lymphopoietin (TSLP) is an epithelial cell-derived cytokine that strongly activates dendritic cells (DC) and can initiate allergic inflammation. The factors inducing the production of human TSLP are not known. In this study, we show that proinflammatory (TNF-alpha or IL-1alpha) and Th2 (IL-4 or IL-13) cytokines synergized to induce the production of TSLP in human skin explants. TSLP production in situ was restricted to epidermal keratinocytes of the suprabasal layer. TSLP production could not be inhibited by factors regulating Th2 inflammation, such as IL-10, TGF-beta, or IFN-gamma. Cytokine-treated skin culture supernatants induced the maturation of blood CD11c(+) DC in a TSLP-dependent manner. Our data provide the first evidence of TSLP induction and subsequent DC activation in human skin. Blocking TSLP-inducing cytokines could represent a novel strategy for the treatment of allergic diseases.