Th17-associated cytokines IL-17 and IL-23 in inflamed skin of Darier disease patients as potential therapeutic targets.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
17 11 2023
17 11 2023
Historique:
received:
05
01
2023
accepted:
02
11
2023
medline:
20
11
2023
pubmed:
18
11
2023
entrez:
18
11
2023
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 37978298
doi: 10.1038/s41467-023-43210-5
pii: 10.1038/s41467-023-43210-5
pmc: PMC10656568
doi:
Substances chimiques
Interleukin-17
0
Interleukin-23
0
Sarcoplasmic Reticulum Calcium-Transporting ATPases
EC 3.6.3.8
IL23A protein, human
0
IL17A protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
7470Informations de copyright
© 2023. The Author(s).
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