Active juvenile systemic lupus erythematosus is associated with distinct NK cell transcriptional and phenotypic alterations.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
06 06 2024
06 06 2024
Historique:
received:
07
07
2023
accepted:
15
05
2024
medline:
7
6
2024
pubmed:
7
6
2024
entrez:
6
6
2024
Statut:
epublish
Résumé
While adaptive immune responses have been studied extensively in SLE (systemic lupus erythematosus), there is limited and contradictory evidence regarding the contribution of natural killer (NK) cells to disease pathogenesis. There is even less evidence about the role of NK cells in the more severe phenotype with juvenile-onset (J)SLE. In this study, analysis of the phenotype and function of NK cells in a large cohort of JSLE patients demonstrated that total NK cells, as well as perforin and granzyme A expressing NK cell populations, were significantly diminished in JSLE patients compared to age- and sex-matched healthy controls. The reduction in NK cell frequency was associated with increased disease activity, and transcriptomic analysis of NK populations from active and low disease activity JSLE patients versus healthy controls confirmed that disease activity was the main driver of differential NK cell gene expression. Pathway analysis of differentially expressed genes revealed an upregulation of interferon-α responses and a downregulation of exocytosis in active disease compared to healthy controls. Further gene set enrichment analysis also demonstrated an overrepresentation of the apoptosis pathway in active disease. This points to increased propensity for apoptosis as a potential factor contributing to NK cell deficiency in JSLE.
Identifiants
pubmed: 38844784
doi: 10.1038/s41598-024-62325-3
pii: 10.1038/s41598-024-62325-3
doi:
Substances chimiques
Granzymes
EC 3.4.21.-
Perforin
126465-35-8
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
13074Subventions
Organisme : RCUK | MRC | Medical Research Foundation
ID : MRF-057-0001-RG-ROSS-C0797
Organisme : DH | National Institute for Health Research (NIHR)
ID : BRC773/III/CC/101350
Informations de copyright
© 2024. The Author(s).
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