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Axl and MerTK regulate synovial inflammation and are modulated by IL-6 inhibition in rheumatoid arthritis.
Nerviani, Alessandra; Boutet, Marie-Astrid; Ghirardi, Giulia Maria; Goldmann, Katriona; Sciacca, Elisabetta; Rivellese, Felice; Pontarini, Elena; Prediletto, Edoardo; Abatecola, Federico; Caliste, Mattia; Pagani, Sara; Mauro, Daniele; Bellan, Mattia; Cubuk, Cankut; Lau, Rachel; Church, Sarah E; Hudson, Briana M; Humby, Frances; Bombardieri, Michele; Lewis, Myles J; Pitzalis, Costantino.
Afiliación
  • Nerviani A; Centre for Experimental Medicine and Rheumatology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London & NIHR BRC Barts Health NHS Trust, London, UK.
  • Boutet MA; Centre for Experimental Medicine and Rheumatology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London & NIHR BRC Barts Health NHS Trust, London, UK.
  • Ghirardi GM; Nantes Université, Oniris, INSERM, Regenerative Medicine and Skeleton, RMeS, UMR 1229, F-44000, Nantes, France.
  • Goldmann K; Centre for Experimental Medicine and Rheumatology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London & NIHR BRC Barts Health NHS Trust, London, UK.
  • Sciacca E; Centre for Experimental Medicine and Rheumatology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London & NIHR BRC Barts Health NHS Trust, London, UK.
  • Rivellese F; Centre for Experimental Medicine and Rheumatology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London & NIHR BRC Barts Health NHS Trust, London, UK.
  • Pontarini E; Centre for Experimental Medicine and Rheumatology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London & NIHR BRC Barts Health NHS Trust, London, UK.
  • Prediletto E; Centre for Experimental Medicine and Rheumatology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London & NIHR BRC Barts Health NHS Trust, London, UK.
  • Abatecola F; Centre for Experimental Medicine and Rheumatology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London & NIHR BRC Barts Health NHS Trust, London, UK.
  • Caliste M; Centre for Experimental Medicine and Rheumatology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London & NIHR BRC Barts Health NHS Trust, London, UK.
  • Pagani S; Centre for Experimental Medicine and Rheumatology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London & NIHR BRC Barts Health NHS Trust, London, UK.
  • Mauro D; Centre for Experimental Medicine and Rheumatology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London & NIHR BRC Barts Health NHS Trust, London, UK.
  • Bellan M; Centre for Experimental Medicine and Rheumatology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London & NIHR BRC Barts Health NHS Trust, London, UK.
  • Cubuk C; Centre for Experimental Medicine and Rheumatology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London & NIHR BRC Barts Health NHS Trust, London, UK.
  • Lau R; Department of Rheumatology, University of Eastern Piedmont and Maggiore della Carita Hospital, Novara, Italy.
  • Church SE; Centre for Experimental Medicine and Rheumatology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London & NIHR BRC Barts Health NHS Trust, London, UK.
  • Hudson BM; Centre for Experimental Medicine and Rheumatology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London & NIHR BRC Barts Health NHS Trust, London, UK.
  • Humby F; NanoString Technologies Inc, Seattle, WA, USA.
  • Bombardieri M; NanoString Technologies Inc, Seattle, WA, USA.
  • Lewis MJ; Centre for Experimental Medicine and Rheumatology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London & NIHR BRC Barts Health NHS Trust, London, UK.
  • Pitzalis C; Centre for Experimental Medicine and Rheumatology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London & NIHR BRC Barts Health NHS Trust, London, UK.
Nat Commun ; 15(1): 2398, 2024 Mar 16.
Article en En | MEDLINE | ID: mdl-38493215
ABSTRACT
The TAM tyrosine kinases, Axl and MerTK, play an important role in rheumatoid arthritis (RA). Here, using a unique synovial tissue bioresource of patients with RA matched for disease stage and treatment exposure, we assessed how Axl and MerTK relate to synovial histopathology and disease activity, and their topographical expression and longitudinal modulation by targeted treatments. We show that in treatment-naive patients, high AXL levels are associated with pauci-immune histology and low disease activity and inversely correlate with the expression levels of pro-inflammatory genes. We define the location of Axl/MerTK in rheumatoid synovium using immunohistochemistry/fluorescence and digital spatial profiling and show that Axl is preferentially expressed in the lining layer. Moreover, its ectodomain, released in the synovial fluid, is associated with synovial histopathology. We also show that Toll-like-receptor 4-stimulated synovial fibroblasts from patients with RA modulate MerTK shedding by macrophages. Lastly, Axl/MerTK synovial expression is influenced by disease stage and therapeutic intervention, notably by IL-6 inhibition. These findings suggest that Axl/MerTK are a dynamic axis modulated by synovial cellular features, disease stage and treatment.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Artritis Reumatoide / Proteínas Tirosina Quinasas Receptoras Límite: Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2024 Tipo del documento: Article Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Artritis Reumatoide / Proteínas Tirosina Quinasas Receptoras Límite: Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2024 Tipo del documento: Article Pais de publicación: Reino Unido