{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:28:27Z","timestamp":1792787307237,"version":"4.5.0"},"reference-count":46,"publisher":"BMJ","issue":"4","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Union","award":["847551"],"award-info":[{"award-number":["847551"]}],"id":[{"id":"https:\/\/ror.org\/019w4f821","id-type":"ROR","asserted-by":"crossref"}]},{"name":"ZonMw VIDI","award":["917183711"],"award-info":[{"award-number":["917183711"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["RMD Open"],"accepted":{"date-parts":[[2026,9,21]]},"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Cellular ageing of the immune system has been suggested to play a role in the pathogenesis of rheumatoid arthritis (RA). RA onset is preceded by a preclinical phase of systemic autoimmunity without overt tissue inflammation, allowing the investigation of predisease cellular dysfunction in at-risk individuals. Lymph nodes (LNs) are crucial for (auto)antibody development, with LN fibroblasts playing a key role in regulating immune homeostasis. Here, we investigated age-associated alterations in LN fibroblast differentiation capacity during the at-risk and established stages of RA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Primary LN fibroblasts were isolated from inguinal LN core biopsies obtained from healthy controls, at-risk individuals and patients with RA. Adipogenic differentiation assays served as a functional readout of cellular plasticity and bulk RNA sequencing was used to evaluate ageing-related transcriptional changes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      LN fibroblasts from at-risk individuals and patients with RA exhibited reduced adipogenic capacity, reflected by fewer lipid droplet-positive cells on differentiation. Transcriptomic analysis revealed downregulation of cell cycle, DNA repair and differentiation pathways. These fibroblasts also failed to upregulate the cell cycle switch\n                      <jats:italic>G0S2<\/jats:italic>\n                      on stimulation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Together, these findings indicate a disrupted coordination between cell cycle processes and differentiation in at-risk and RA LN fibroblasts, consistent with features of cellular ageing. Notably, these alterations were already present in at-risk individuals prior to clinical disease onset, suggesting that reduced fibroblast fitness may contribute to impaired LN tissue homeostasis in disease-prone individuals.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/rmdopen-2026-007143","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T13:39:44Z","timestamp":1790861984000},"page":"e007143","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Early features of cellular ageing impair differentiation capacity in human lymph node fibroblasts prior to rheumatoid arthritis onset"],"prefix":"10.1136","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8483-5539","authenticated-orcid":false,"given":"Marina","family":"Jim\u00e9nez-Mart\u00ednez","sequence":"first","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Amsterdam UMC, location AMC, University of Amsterdam, Amsterdam, The Netherlands"},{"name":"Amsterdam Rheumatology and Immunology Center (ARC), Amsterdam, The Netherlands"},{"name":"Amsterdam Institute for Immunology and Infectious Diseases, Amsterdam, The Netherlands"},{"name":"Amsterdam Movement Sciences, Amsterdam UMC, location AMC, University of Amsterdam, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tineke A","family":"De Jong","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Amsterdam UMC, location AMC, University of Amsterdam, Amsterdam, The Netherlands"},{"name":"Amsterdam Rheumatology and Immunology Center (ARC), Amsterdam, The Netherlands"},{"name":"Amsterdam Institute for Immunology and Infectious Diseases, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miranda","family":"Houtman","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Amsterdam UMC, location AMC, University of Amsterdam, Amsterdam, The Netherlands"},{"name":"Amsterdam Rheumatology and Immunology Center (ARC), Amsterdam, The Netherlands"},{"name":"Amsterdam Institute for Immunology and Infectious Diseases, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanna F","family":"Semmelink","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Amsterdam UMC, location AMC, University of Amsterdam, Amsterdam, The Netherlands"},{"name":"Amsterdam Rheumatology and Immunology Center (ARC), Amsterdam, The Netherlands"},{"name":"Amsterdam Institute for Immunology and Infectious Diseases, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noam","family":"Zelcer","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Amsterdam UMC, Amsterdam, The Netherlands"},{"name":"Amsterdam Cardiovascular Sciences (ACS), University of Amsterdam, Amsterdam, The Netherlands"},{"name":"Gastroenterology and Metabolism (AGEM), University of Amsterdam, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0966-878X","authenticated-orcid":false,"given":"Marleen G H","family":"van de Sande","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Amsterdam UMC, location AMC, University of Amsterdam, Amsterdam, The Netherlands"},{"name":"Amsterdam Rheumatology and Immunology Center (ARC), Amsterdam, The Netherlands"},{"name":"Amsterdam Institute for Immunology and Infectious Diseases, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendy","family":"Dankers","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Amsterdam UMC, location AMC, University of Amsterdam, Amsterdam, The 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