Neutrophil dysregulation is pathogenic in idiopathic inflammatory myopathies - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue JCI Insight Année : 2020

Neutrophil dysregulation is pathogenic in idiopathic inflammatory myopathies

Catia Fernandes-Cerqueira
  • Fonction : Auteur
Diana Gómez-Martín
Albert Selva-O’callaghan
  • Fonction : Auteur
Josep Grau-Junyent
  • Fonction : Auteur
Lisa Christopher-Stine
  • Fonction : Auteur
Ingrid Lundberg
J. Michelle Kahlenberg

Résumé

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
Fichier principal
Vignette du fichier
jci.insight.134189.v2.pdf (5.43 Mo) Télécharger le fichier
Origine Fichiers éditeurs autorisés sur une archive ouverte

Dates et versions

hal-03831101 , version 1 (15-11-2022)

Identifiants

Citer

Nickie Seto, Jose Jiram Torres-Ruiz, Carmelo Carmona-Rivera, Iago Pinal-Fernandez, Katherine Pak, et al.. Neutrophil dysregulation is pathogenic in idiopathic inflammatory myopathies. JCI Insight, 2020, 5 (3), pp.e134189. ⟨10.1172/jci.insight.134189⟩. ⟨hal-03831101⟩
12 Consultations
48 Téléchargements

Altmetric

Partager

Gmail Mastodon Facebook X LinkedIn More