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

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 Tsai, Suraj R. Varkhande, Leonie C. Schoeftner, Christoph Iselin, Iris K. Gratz, Susanne Kimeswenger, Emmanuella Guenova and Wolfram Hoetzenecker ()
Additional contact information
Monika Ettinger: Kepler University Hospital 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
Rupert Langer: Kepler University Hospital 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
Wolfram Hoetzenecker: Kepler University Hospital Linz

Nature Communications, 2023, vol. 14, issue 1, 1-10

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-43210-5

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