Coordinated local RNA overexpression of complement induced by interferon gamma in myositis.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
04 02 2023
04 02 2023
Historique:
received:
01
12
2022
accepted:
25
01
2023
entrez:
4
2
2023
pubmed:
5
2
2023
medline:
8
2
2023
Statut:
epublish
Résumé
Complement proteins are deposited in the muscles of patients with myositis. However, the local expression and regulation of complement genes within myositis muscle have not been well characterized. In this study, bulk RNA sequencing (RNAseq) analyses of muscle biopsy specimens revealed that complement genes are locally overexpressed and correlate with markers of myositis disease activity, including the expression of interferon-gamma (IFNγ)-induced genes. Single cell and single nuclei RNAseq analyses showed that most local expression of complement genes occurs in macrophages, fibroblasts, and satellite cells, with each cell type expressing different sets of complement genes. Biopsies from immune-mediated necrotizing myopathy patients, who have the lowest levels of IFNγ-induced genes, also had the lowest complement gene expression levels. Furthermore, data from cultured human cells showed that IFNγ upregulates complement expression in macrophages, fibroblasts, and muscle cells. Taken together, our results suggest that in myositis muscle, IFNγ coordinates the local overexpression of complement genes that occurs in several cell types.
Identifiants
pubmed: 36739295
doi: 10.1038/s41598-023-28838-z
pii: 10.1038/s41598-023-28838-z
pmc: PMC9899209
doi:
Substances chimiques
Complement System Proteins
9007-36-7
Interferon-gamma
82115-62-6
RNA
63231-63-0
IFNG protein, human
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
2038Informations de copyright
© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.
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