Cutting edge: proinflammatory and Th2 cytokines synergize to induce thymic stromal lymphopoietin production by human skin keratinocytes

SI Bogiatzi, I Fernandez, JC Bichet… - The Journal of …, 2007 - journals.aai.org
SI Bogiatzi, I Fernandez, JC Bichet, MA Marloie-Provost, E Volpe, X Sastre, V Soumelis
The Journal of Immunology, 2007journals.aai.org
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-
α or IL-1α) 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 …
Abstract
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-α or IL-1α) 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-β, or IFN-γ. 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.
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