TY - JOUR
T1 - Coordinated local RNA overexpression of complement induced by interferon gamma in myositis
AU - Casal-Dominguez, Maria
AU - Pinal-Fernandez, Iago
AU - Pak, Katherine
AU - Muñoz-Braceras, Sandra
AU - Milisenda, Jose C.
AU - Torres-Ruiz, Jiram
AU - Dell′Orso, Stefania
AU - Naz, Faiza
AU - Gutierrez-Cruz, Gustavo
AU - Duque-Jaimez, Yaiza
AU - Matas-Garcia, Ana
AU - Valls-Roca, Laura
AU - Garrabou, Gloria
AU - Trallero-Araguas, Ernesto
AU - Walitt, Brian
AU - Christopher-Stine, Lisa
AU - Lloyd, Thomas E.
AU - Paik, Julie J.
AU - Albayda, Jemima
AU - Corse, Andrea
AU - Grau, Josep Maria
AU - Selva-O’Callaghan, Albert
AU - Mammen, Andrew L.
N1 - Funding Information:
This study was funded, in part, by the Intramural Research Program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health.
Funding Information:
Open Access funding provided by the National Institutes of Health (NIH).
Publisher Copyright:
© 2023, This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.
PY - 2023/12
Y1 - 2023/12
N2 - 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.
AB - 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.
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U2 - 10.1038/s41598-023-28838-z
DO - 10.1038/s41598-023-28838-z
M3 - Article
C2 - 36739295
AN - SCOPUS:85147392728
SN - 2045-2322
VL - 13
JO - Scientific reports
JF - Scientific reports
IS - 1
M1 - 2038
ER -