Coordinated local RNA overexpression of complement induced by interferon gamma in myositis
Casal-Dominguez, Maria (Johns Hopkins University School of Medicine)
Pinal-Fernandez, Iago (Johns Hopkins University School of Medicine)
Pak, Katherine (National Institute of Arthritis and Musculoskeletal and Skin Diseases)
Muñoz-Braceras, Sandra (National Institute of Arthritis and Musculoskeletal and Skin Diseases)
Milisenda, Jose C. (Hospital Clínic i Provincial de Barcelona)
Torres-Ruiz, Jiram (Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán)
Dell'Orso, Stefania (National Institute of Arthritis and Musculoskeletal and Skin Diseases)
Naz, Faiza (National Institute of Arthritis and Musculoskeletal and Skin Diseases)
Gutierrez-Cruz, Gustavo (National Institute of Arthritis and Musculoskeletal and Skin Diseases)
Duque-Jaimez, Yaiza (Hospital Clínic i Provincial de Barcelona)
Matas-Garcia, Ana (Hospital Clínic i Provincial de Barcelona)
Valls-Roca, Laura (Hospital Clínic i Provincial de Barcelona)
Garrabou, Glòria (Hospital Clínic i Provincial de Barcelona)
Trallero-Araguas, Ernesto (Hospital Universitari Vall d'Hebron)
Walitt, Brian (National Institute of Neurological Disorders and Stroke)
Christopher-Stine, Lisa (Johns Hopkins University School of Medicine)
Lloyd, Thomas E. (Johns Hopkins University School of Medicine)
Paik, Julie J. (Johns Hopkins University School of Medicine)
Albayda, Jemima (Johns Hopkins University School of Medicine)
Corse, Andrea (Johns Hopkins University School of Medicine)
Grau, Josep Maria (Hospital Clínic i Provincial de Barcelona)
Selva O'Callaghan, Albert (Universitat Autònoma de Barcelona)
Mammen, Andrew L. (Johns Hopkins University School of Medicine)

Date:	2023
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.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Autoimmunity ; Complement cascade ; Immunology ; Immunological disorders ; Autoimmune diseases
Published in:	Scientific reports, Vol. 13 (february 2023) , ISSN 2045-2322

DOI: 10.1038/s41598-023-28838-z
PMID: 36739295

10 p, 1.3 MB

The record appears in these collections:
Articles > Research articles
Articles > Published articles