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

Albert Selva O'Callaghan, Maria Casal-Dominguez, Iago Pinal-Fernandez, Katherine Pak, Sandra Muñoz-Braceras, Jose C. Milisenda, Jiram Torres-Ruiz, Stefania Dell'Orso, Faiza Naz, Gustavo Gutierrez-Cruz, Yaiza Duque-Jaimez, Ana Matas-Garcia, Laura Valls-Roca, Gloria Garrabou, Ernesto Trallero-Araguas, Brian Walitt, Lisa Christopher-Stine, Thomas E. Lloyd, Julie J. Paik, Jemima AlbaydaAndrea Corse, Josep Maria Grau, Andrew L. Mammen

Research output: Contribution to journalArticleResearchpeer-review

Abstract

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.
Original languageEnglish
Article number2038
Number of pages10
JournalScientific Reports
Volume13
DOIs
Publication statusPublished - 4 Feb 2023

Keywords

  • Autoimmunity
  • Complement cascade
  • Immunology
  • Immunological disorders
  • Autoimmune diseases

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