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

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Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_D062CF696E69
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Th17-associated cytokines IL-17 and IL-23 in inflamed skin of Darier disease patients as potential therapeutic targets.
Journal
Nature communications
Author(s)
Ettinger M., Burner T., Sharma A., Chang Y.T., Lackner A., Prompsy P., Deli I.M., Traxler J., Wahl G., Altrichter S., Langer R., Tsai Y.C., Varkhande S.R., Schoeftner L.C., Iselin C., Gratz I.K., Kimeswenger S., Guenova E., Hoetzenecker W.
ISSN
2041-1723 (Electronic)
ISSN-L
2041-1723
Publication state
Published
Issued date
17/11/2023
Peer-reviewed
Oui
Volume
14
Number
1
Pages
7470
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
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.
Keywords
Humans, Darier Disease/genetics, Darier Disease/metabolism, Darier Disease/pathology, Interleukin-17/genetics, Interleukin-17/metabolism, Interleukin-23/metabolism, Sarcoplasmic Reticulum Calcium-Transporting ATPases/metabolism, Skin/pathology, Th17 Cells/metabolism
Pubmed
Web of science
Open Access
Yes
Create date
23/11/2023 15:43
Last modification date
08/08/2024 6:40
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