Open AccessCutting Edge: Proinflammatory and Th2 Cytokines Synergize to Induce Thymic Stromal Lymphopoietin Production by Human Skin Keratinocytes
Author(s) -
Sofia Bogiatzi,
Isabel M. Fernandez,
Jean Christophe Bichet,
Marie Annick Marloie-Provost,
Elisabetta Volpe,
Xavier Sastre,
Vassili Soumelis
Publication year - 2007
Publication title -
the journal of immunology/the journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.737
H-Index - 372
eISSN - 1550-6606
pISSN - 0022-1767
DOI - 10.4049/jimmunol.178.6.3373
Subject(s) - thymic stromal lymphopoietin , proinflammatory cytokine , cytokine , immunology , inflammation , human skin , allergic inflammation , interleukin , microbiology and biotechnology , biology , genetics
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.