Coordinated local RNA overexpression of complement induced by interferon gamma in myositis

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 compleme...

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Detalles Bibliográficos
Autores: Casal-Dominguez, Maria, Pinal Fernandez, Iago|||0000-0001-6338-9218, Pak, Katherine, Muñoz-Braceras, Sandra, Milisenda, José César|||0000-0003-0151-7872, Torres-Ruiz, Jiram, Dell'Orso, Stefania, Naz, Faiza, Gutierrez-Cruz, Gustavo, Duque-Jaimez, Yaiza, Matas-Garcia, Ana|||0000-0002-9184-8079, Valls-Roca, Laura|||0000-0001-5956-6752, Garrabou, Glòria|||0000-0001-8973-9933, Trallero Araguás, Ernesto|||0000-0003-3365-4521, Walitt, Brian, Christopher-Stine, Lisa, Lloyd, Thomas E.|||0000-0003-4756-3700, Paik, Julie J., Albayda, Jemima, Corse, Andrea, Grau, Josep Maria, Selva O'Callaghan, Albert|||0000-0003-2823-9761, Mammen, Andrew L.|||0000-0003-3732-3252
Tipo de recurso: artículo
Fecha de publicación:2023
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:273933
Acceso en línea:https://ddd.uab.cat/record/273933
https://dx.doi.org/urn:doi:10.1038/s41598-023-28838-z
Access Level:acceso abierto
Palabra clave:Autoimmunity
Complement cascade
Immunology
Immunological disorders
Autoimmune diseases
Descripción
Sumario: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 (IFN γ)-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 IFN γ -induced genes, also had the lowest complement gene expression levels. Furthermore, data from cultured human cells showed that IFN γ upregulates complement expression in macrophages, fibroblasts, and muscle cells. Taken together, our results suggest that in myositis muscle, IFN γ coordinates the local overexpression of complement genes that occurs in several cell types.

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