Cutting Edge: Proinflammatory and Th2 cytokines synergize to induce thymic stromal lymphopoietin production by human skin keratinocytes.
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.
Bogiatzi
Sofia I
SI
Institut National de la Santé et de la Recherche Médicale U653 and Laboratoire d'Immunologie Clinique, Institut Curie, 26 rue d'Ulm, 75005 Paris, France.
Fernandez
Isabel
I
Bichet
Jean-Christophe
JC
Marloie-Provost
Marie-Annick
MA
Volpe
Elisabetta
E
Sastre
Xavier
X
Soumelis
Vassili
V
D000328:Adult; D000368:Aged; D039521:CD11c Antigen / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000819:agonists* / Q000096:biosynthesis / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology / Q000378:metabolism / Q000628:therapy; D018836:Inflammation Mediators / Q000819:agonists* / Q000276:immunology; D015603:Keratinocytes / Q000276:immunology* / Q000378:metabolism; D008875:Middle Aged; D015398:Signal Transduction / Q000276:immunology; D012867:Skin / Q000276:immunology* / Q000378:metabolism; D000094632:Thymic Stromal Lymphopoietin
D039521:CD11c Antigen; D016207:Cytokines; D018836:Inflammation Mediators; D000094632:Thymic Stromal Lymphopoietin