Thymic stromal lymphopoietin links keratinocytes and dendritic cell-derived IL-23 in patients with psoriasis

Elisabetta Volpe, Lucia Pattarini, Carolina Martinez-Cingolani, Stephan Meller, Marie Helene Donnadieu, Sofia I. Bogiatzi, Maria I. Fernandez, Maxime Touzot, Jean Christophe Bichet, Fabien Reyal, Maria Paola Paronetto, Andrea Chiricozzi, Sergio Chimenti, Francesca Nasorri, Andrea Cavani, Andreas Kislat, Bernhard Homey, Vassili Soumelis

Research output: Contribution to journalArticlepeer-review

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. Conclusion 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.

Original languageEnglish
JournalJournal of Allergy and Clinical Immunology
Volume134
Issue number2
DOIs
Publication statusPublished - 2014

Keywords

  • CD40 ligand
  • dendritic cells
  • IL-23
  • psoriasis
  • skin inflammation
  • Thymic stromal lymphopoietin

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Medicine(all)

Fingerprint Dive into the research topics of 'Thymic stromal lymphopoietin links keratinocytes and dendritic cell-derived IL-23 in patients with psoriasis'. Together they form a unique fingerprint.

Cite this