dc.contributor.author | Nerviani, A | en_US |
dc.contributor.author | Boutet, M-A | en_US |
dc.contributor.author | Ghirardi, GM | en_US |
dc.contributor.author | Goldmann, K | en_US |
dc.contributor.author | Sciacca, E | en_US |
dc.contributor.author | Rivellese, F | en_US |
dc.contributor.author | Pontarini, E | en_US |
dc.contributor.author | Prediletto, E | en_US |
dc.contributor.author | Abatecola, F | en_US |
dc.contributor.author | Caliste, M | en_US |
dc.contributor.author | Pagani, S | en_US |
dc.contributor.author | Mauro, D | en_US |
dc.contributor.author | Bellan, M | en_US |
dc.contributor.author | Cubuk, C | en_US |
dc.contributor.author | Lau, R | en_US |
dc.contributor.author | Church, SE | en_US |
dc.contributor.author | Hudson, BM | en_US |
dc.contributor.author | Humby, F | en_US |
dc.contributor.author | Bombardieri, M | en_US |
dc.contributor.author | Lewis, MJ | en_US |
dc.contributor.author | Pitzalis, C | en_US |
dc.date.accessioned | 2024-03-27T09:17:05Z | |
dc.date.available | 2024-02-27 | en_US |
dc.date.issued | 2024-03-16 | en_US |
dc.identifier.uri | https://qmro.qmul.ac.uk/xmlui/handle/123456789/95783 | |
dc.description.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. | en_US |
dc.format.extent | 2398 - ? | en_US |
dc.language | eng | en_US |
dc.relation.ispartof | Nat Commun | en_US |
dc.rights | This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. | |
dc.subject | Humans | en_US |
dc.subject | Arthritis, Rheumatoid | en_US |
dc.subject | Axl Receptor Tyrosine Kinase | en_US |
dc.subject | c-Mer Tyrosine Kinase | en_US |
dc.subject | Inflammation | en_US |
dc.subject | Interleukin-6 | en_US |
dc.subject | Proto-Oncogene Proteins | en_US |
dc.subject | Receptor Protein-Tyrosine Kinases | en_US |
dc.subject | Synovial Membrane | en_US |
dc.title | Axl and MerTK regulate synovial inflammation and are modulated by IL-6 inhibition in rheumatoid arthritis. | en_US |
dc.type | Article | |
dc.rights.holder | © The Author(s) 2024 | |
dc.identifier.doi | 10.1038/s41467-024-46564-6 | en_US |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/38493215 | en_US |
pubs.issue | 1 | en_US |
pubs.notes | Not known | en_US |
pubs.publication-status | Published online | en_US |
pubs.volume | 15 | en_US |
dcterms.dateAccepted | 2024-02-27 | en_US |
rioxxterms.funder | Default funder | en_US |
rioxxterms.identifier.project | Default project | en_US |
qmul.funder | Synovial B cells inform treatment response in RA (SyBRA)::National Institute of Health Research (NIHR) | en_US |
qmul.funder | Synovial B cells inform treatment response in RA (SyBRA)::National Institute of Health Research (NIHR) | en_US |
qmul.funder | Synovial B cells inform treatment response in RA (SyBRA)::National Institute of Health Research (NIHR) | en_US |