title: Thymic stromal lymphopoietin links keratinocytes and dendritic cell-derived IL-23 in patients with psoriasis.
abstract: BACKGROUND
  Thymic stromal lymphopoietin (TSLP) is a major proallergic cytokine that promotes TH2 responses through dendritic cell (DC) activation. Whether it also plays a role in human autoimmune inflammation and associated pathways is not known.
  
  
  OBJECTIVE
  In this study we investigated the potential role of several epithelium-derived factors, including TSLP, in inducing IL-23 production by human DCs. We further dissected the role of TSLP in patients with psoriasis, an IL-23-associated skin autoimmune disease.
  
  
  METHODS
  The study was performed in human subjects using primary cells and tissue samples from patients with psoriasis and healthy donors. We analyzed the production of IL-23 in vitro by blood and skin DCs. We studied the function for TSLP and its interaction with other components of the inflammatory microenvironment in situ and ex vivo.
  
  
  RESULTS
  We found that TSLP synergized with CD40 ligand to promote DC activation and pathogenic IL-23 production by primary blood and skin DCs. In situ TSLP was strongly expressed by keratinocytes of untreated psoriatic lesions but not in normal skin. Moreover, we could demonstrate that IL-4, an important component of the TH2 inflammation seen in patients with atopic dermatitis, inhibited IL-23 production induced by TSLP and CD40 ligand in a signal transducer and activator of transcription 6-independent manner.
  
  
  CONCLUSIONS
  Our results identify TSLP as a novel player within the complex psoriasis cytokine network. Blocking TSLP in patients with psoriasis might contribute to decreasing DC activation and shutting down the production of pathogenic IL-23.
authors.affiliation: Department of Immunology, Institut Curie, Paris, France; Laboratory of Neuroimmunology, Fondazione Santa Lucia, Rome, Italy. Electronic address: e.volpe@hsantalucia.it.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Volpe
authors.affiliation: Department of Immunology, Institut Curie, Paris, France; Institut National de la Santé et de la Recherche Médicale U932, Paris, France; Research Section, Institut Curie, Paris, France.
authors.forename: Lucia
authors.initials: L
authors.lastname: Pattarini
authors.affiliation: Department of Immunology, Institut Curie, Paris, France; Institut National de la Santé et de la Recherche Médicale U932, Paris, France; Research Section, Institut Curie, Paris, France.
authors.forename: Carolina
authors.initials: C
authors.lastname: Martinez-Cingolani
authors.affiliation: Department of Dermatology, Heinrich Heine University, Düsseldorf, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Meller
authors.affiliation: Department of Immunology, Institut Curie, Paris, France; Institut National de la Santé et de la Recherche Médicale U932, Paris, France.
authors.forename: Marie-Helene
authors.initials: MH
authors.lastname: Donnadieu
authors.affiliation: Department of Immunology, Institut Curie, Paris, France; Institut National de la Santé et de la Recherche Médicale U932, Paris, France.
authors.forename: Sofia I
authors.initials: SI
authors.lastname: Bogiatzi
authors.affiliation: Department of Immunology, Institut Curie, Paris, France; Institut National de la Santé et de la Recherche Médicale U932, Paris, France; Department of Microbiology, Infectiology and Immunology, CHU Sainte-Justine and University of Montreal, Montreal, Quebec, Canada; CHU Sainte-Justine Research Center, Montreal, Quebec, Canada.
authors.forename: Maria I
authors.initials: MI
authors.lastname: Fernandez
authors.affiliation: Department of Immunology, Institut Curie, Paris, France; Institut National de la Santé et de la Recherche Médicale U932, Paris, France.
authors.forename: Maxime
authors.initials: M
authors.lastname: Touzot
authors.affiliation: Départment de Chirurgie, Hopital Pitié Salpétrière, Paris, France.
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Bichet
authors.affiliation: Department of Surgery, Institut Curie, Paris, France.
authors.forename: Fabien
authors.initials: F
authors.lastname: Reyal
authors.affiliation: Laboratory of Molecular and Cellular Neurobiology, Fondazione Santa Lucia, Rome, Italy.
authors.forename: Maria Paola
authors.initials: MP
authors.lastname: Paronetto
authors.affiliation: Department of Dermatology, University of Rome Tor Vergata, Rome, Italy; Laboratory for Investigative Dermatology, Rockefeller University, New York, NY.
authors.forename: Andrea
authors.initials: A
authors.lastname: Chiricozzi
authors.affiliation: Department of Dermatology, University of Rome Tor Vergata, Rome, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Chimenti
authors.affiliation: Laboratory of Experimental Immunology, IDI-IRCCS, Rome, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Nasorri
authors.affiliation: Laboratory of Experimental Immunology, IDI-IRCCS, Rome, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Cavani
authors.affiliation: Department of Dermatology, Heinrich Heine University, Düsseldorf, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Kislat
authors.affiliation: Department of Dermatology, Heinrich Heine University, Düsseldorf, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Homey
authors.affiliation: Department of Immunology, Institut Curie, Paris, France; Institut National de la Santé et de la Recherche Médicale U932, Paris, France; Research Section, Institut Curie, Paris, France. Electronic address: vassili.soumelis@curie.fr.
authors.forename: Vassili
authors.initials: V
authors.lastname: Soumelis
mesh_terms: D000328:Adult; D023201:CD40 Ligand / Q000235:genetics / Q000276:immunology; D016207:Cytokines / Q000235:genetics / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology; D003876:Dermatitis, Atopic / Q000235:genetics / Q000276:immunology / Q000473:pathology; D005786:Gene Expression Regulation; D006801:Humans; D053759:Interleukin-23 / Q000235:genetics / Q000276:immunology*; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology; D015603:Keratinocytes / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D061251:Primary Cell Culture; D011565:Psoriasis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D050800:STAT6 Transcription Factor / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction; D012867:Skin / Q000276:immunology* / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology / Q000473:pathology; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D016207:Cytokines; C508598:IL4 protein, human; D053759:Interleukin-23; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human; D023201:CD40 Ligand; D015847:Interleukin-4; D000094632:Thymic Stromal Lymphopoietin
keywords: CD40 ligand; IL-23; Thymic stromal lymphopoietin; dendritic cells; psoriasis; skin inflammation