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Cutting Edge: Proinflammatory and Th2 Cytokines Synergize to Induce Thymic Stromal Lymphopoietin Production by Human Skin Keratinocytes¹

Sofia I. Bogiatzi^*, Isabel Fernandez^*, Jean-Christophe Bichet, Marie-Annick Marloie-Provost^*, Elisabetta Volpe^*, Xavier Sastre and Vassili Soumelis^2,*

^* Institut National de la Santé et de la Recherche Médicale U653 and Laboratoire d’Immunologie Clinique, Institut Curie, Paris, France; Institut Curie, Department of Pathology, Paris, France; and Department of Surgery, Hôpital Pitié-Salpétrière, Paris, France

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- or IL-1) 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-, or IFN-. 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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by a Marie Curie Excellence Grant (014162) to V.S. V.S. is supported by an Institut National de la Santé et de la Recherche Médicale Avenir grant.

² Address correspondence and reprint requests to Vassili Soumelis, MD, PhD, Institut National de la Santé et de la Recherche Médicale U653, Institut Curie, 26 rue d’Ulm, 75005 Paris, France. E-mail address: vassili.soumelis{at}curie.net

³ Abbreviations used in this paper: TSLP, thymic stromal lymphopoietin; AD, atopic dermatitis; MFI, mean fluorescence intensity; DC, dendritic cell.

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