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Th17-associated cytokines IL-17 and IL-23 in inflamed skin of Darier disease patients as potential therapeutic targets

Author

Listed:
  • Monika Ettinger

    (Kepler University Hospital Linz
    Medical Faculty, Johannes Kepler University Linz)

  • Teresa Burner

    (Medical Faculty, Johannes Kepler University Linz)

  • Anshu Sharma

    (University of Salzburg)

  • Yun-Tsan Chang

    (University of Lausanne and Faculty of Biology and Medicine)

  • Angelika Lackner

    (Medical Faculty, Johannes Kepler University Linz)

  • Pacôme Prompsy

    (University of Lausanne and Faculty of Biology and Medicine)

  • Isabella M. Deli

    (Kepler University Hospital Linz)

  • Judith Traxler

    (Kepler University Hospital Linz)

  • Gerald Wahl

    (Kepler University Hospital Linz)

  • Sabine Altrichter

    (Kepler University Hospital Linz
    Medical Faculty, Johannes Kepler University Linz)

  • Rupert Langer

    (Kepler University Hospital Linz
    Medical Faculty, Johannes Kepler University Linz)

  • Yi-Chien Tsai

    (University of Lausanne and Faculty of Biology and Medicine)

  • Suraj R. Varkhande

    (University of Salzburg)

  • Leonie C. Schoeftner

    (University of Salzburg)

  • Christoph Iselin

    (University of Lausanne and Faculty of Biology and Medicine)

  • Iris K. Gratz

    (University of Salzburg)

  • Susanne Kimeswenger

    (Medical Faculty, Johannes Kepler University Linz)

  • Emmanuella Guenova

    (University of Lausanne and Faculty of Biology and Medicine
    Hospital 12 de octubre, Medical school, University Complutense)

  • Wolfram Hoetzenecker

    (Kepler University Hospital Linz
    Medical Faculty, Johannes Kepler University Linz)

Abstract

Darier disease (DD) is a rare, inherited multi-organ disorder associated with mutations in the ATP2A2 gene. DD patients often have skin involvement characterized by malodorous, inflamed skin and recurrent, severe infections. Therapeutic options are limited and inadequate for the long-term management of this chronic disease. The aim of this study was to characterize the cutaneous immune infiltrate in DD skin lesions in detail and to identify new therapeutic targets. Using gene and protein expression profiling assays including scRNA sequencing, we demonstrate enhanced expression of Th17-related genes and cytokines and increased numbers of Th17 cells in six DD patients. We provide evidence that targeting the IL-17/IL-23 axis in a case series of three DD patients with monoclonal antibodies is efficacious with significant clinical improvement. As DD is a chronic, relapsing disease, our findings might pave the way toward additional options for the long-term management of skin inflammation in patients with DD.

Suggested Citation

  • Monika Ettinger & Teresa Burner & Anshu Sharma & Yun-Tsan Chang & Angelika Lackner & Pacôme Prompsy & Isabella M. Deli & Judith Traxler & Gerald Wahl & Sabine Altrichter & Rupert Langer & Yi-Chien Tsa, 2023. "Th17-associated cytokines IL-17 and IL-23 in inflamed skin of Darier disease patients as potential therapeutic targets," Nature Communications, Nature, vol. 14(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-43210-5
    DOI: 10.1038/s41467-023-43210-5
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