Neutrophil dysregulation is pathogenic in idiopathic inflammatory myopathies.

Autor: Seto N; Systemic Autoimmunity Branch, Intramural Research Program, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), NIH, Bethesda, Maryland, USA., Torres-Ruiz JJ; Systemic Autoimmunity Branch, Intramural Research Program, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), NIH, Bethesda, Maryland, USA.; Instituto Nacional de Ciencias Medicas y de la Nutrición Salvador Zubiran, Mexico City, México., Carmona-Rivera C; Systemic Autoimmunity Branch, Intramural Research Program, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), NIH, Bethesda, Maryland, USA., Pinal-Fernandez I; Muscle Disease Unit, NIAMS, NIH, Bethesda, Maryland, USA.; Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.; Faculty of Health Sciences and Faculty of Computer Science, Universitat Oberta de Catalunya, Barcelona, Spain., Pak K; Muscle Disease Unit, NIAMS, NIH, Bethesda, Maryland, USA., Purmalek MM; Systemic Autoimmunity Branch, Intramural Research Program, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), NIH, Bethesda, Maryland, USA., Hosono Y; Muscle Disease Unit, NIAMS, NIH, Bethesda, Maryland, USA., Fernandes-Cerqueira C; Division of Rheumatology, Department of Medicine, Solna, Karolinska Institutet, and Rheumatology Clinic, Karolinska University Hospital, Stockholm, Sweden., Gowda P; Infrared Imaging and Thermometry Unit, National Institute of Biomedical Imaging and Bioengineering, NIH, Bethesda, Maryland, USA., Arnett N; Infrared Imaging and Thermometry Unit, National Institute of Biomedical Imaging and Bioengineering, NIH, Bethesda, Maryland, USA., Gorbach A; Infrared Imaging and Thermometry Unit, National Institute of Biomedical Imaging and Bioengineering, NIH, Bethesda, Maryland, USA., Benveniste O; Department of Internal Medicine and Clinical Immunology, CHU Paris-GH La Pitié-Salpêtrière-Charles Foix-Hôpital Pitié Salpêtrière, Paris, France., Gómez-Martín D; Instituto Nacional de Ciencias Medicas y de la Nutrición Salvador Zubiran, Mexico City, México., Selva-O'Callaghan A; Hospital General Universitario Vall d'Hebron, Universidad Autónoma de Barcelona, Barcelona, Spain., Milisenda JC; Hospital Clinic de Barcelona and Universidad de Barcelona, Barcelona, Spain., Grau-Junyent JM; Hospital Clinic de Barcelona and Universidad de Barcelona, Barcelona, Spain., Christopher-Stine L; Johns Hopkins University School of Medicine, Baltimore, Maryland, USA., Miller FW; Environmental Autoimmunity Group, Clinical Research Branch, National Institute of Environmental Health Sciences (NIEHS), NIH, Research Triangle Park, North Carolina and Bethesda, Maryland, USA., Lundberg IE; Division of Rheumatology, Department of Medicine, Solna, Karolinska Institutet, and Rheumatology Clinic, Karolinska University Hospital, Stockholm, Sweden., Kahlenberg JM; Division of Rheumatology, University of Michigan Medical School, Ann Arbor, Michigan, USA., Schiffenbauer AI; Environmental Autoimmunity Group, Clinical Research Branch, National Institute of Environmental Health Sciences (NIEHS), NIH, Bethesda, Maryland, USA., Mammen A; Muscle Disease Unit, NIAMS, NIH, Bethesda, Maryland, USA.; Johns Hopkins University School of Medicine, Baltimore, Maryland, USA., Rider LG; Environmental Autoimmunity Group, Clinical Research Branch, National Institute of Environmental Health Sciences (NIEHS), NIH, Bethesda, Maryland, USA., Kaplan MJ; Systemic Autoimmunity Branch, Intramural Research Program, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), NIH, Bethesda, Maryland, USA.
Jazyk: angličtina
Zdroj: JCI insight [JCI Insight] 2020 Feb 13; Vol. 5 (3). Date of Electronic Publication: 2020 Feb 13.
DOI: 10.1172/jci.insight.134189
Abstrakt: Idiopathic inflammatory myopathies (IIM) are characterized by muscle inflammation and weakness, myositis-specific autoantibodies (MSAs), and extramuscular organ damage. The role of neutrophil dysregulation and neutrophil extracellular traps (NETs) in IIM is unclear. We assessed whether pathogenic neutrophil subsets (low-density granulocytes [LDGs]) and NETs were elevated in IIM, associated with clinical presentation and MSAs, and their effect on skeletal myoblasts and myotubes. Circulating NETs and LDGs were quantified and correlated with clinical measures. Specific MSAs were tested for their ability to induce NETs. NETs and neutrophil gene expression were measured in IIM biopsies. Whether NETs damage skeletal myoblasts and myotubes was tested. Circulating LDGs and NETs were increased in IIM. IIM LDGs had an enhanced ability to form NETs. LDGs and NETs correlated with IIM disease activity and muscle damage. The serum MSA anti-MDA5 correlated with circulating and tissue NETs and directly enhanced NET formation. An enhanced neutrophil gene signature was present in IIM muscle and associated with muscle injury and tissue IFN gene signatures. IIM NETs decreased the viability of myotubes in a citrullinated histone-dependent manner. Dysregulated neutrophil pathways may play pathogenic roles in IIM through their ability to directly injure muscle cells and other affected tissues.
Databáze: MEDLINE