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Ettinger, Monika; Burner, Teresa; Sharma, Anshu; Chang, Yun-Tsan; Lackner, Angelika; Prompsy, Pacôme; Deli, Isabella M; Traxler, Judith; Wahl, Gerald; Altrichter, Sabine; Langer, Rupert; Tsai, Yi-Chien; Varkhande, Suraj R; Schoeftner, Leonie C; Iselin, Christoph; Gratz, Iris K; Kimeswenger, Susanne; Guenova, Emmanuella; Hoetzenecker, Wolfram
Nature communications, 11/2023, Letnik: 14, Številka: 1Journal Article
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.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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in: SICRIS
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