{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T21:06:06Z","timestamp":1781989566433,"version":"3.54.5"},"reference-count":47,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T00:00:00Z","timestamp":1771286400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T00:00:00Z","timestamp":1771286400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81902947"],"award-info":[{"award-number":["81902947"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82372789"],"award-info":[{"award-number":["82372789"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82572070"],"award-info":[{"award-number":["82572070"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018542","name":"Natural Science Foundation of Sichuan Province","doi-asserted-by":"publisher","award":["2024NSFSC1760"],"award-info":[{"award-number":["2024NSFSC1760"]}],"id":[{"id":"10.13039\/501100018542","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>We investigated tumor necrosis factor (TNF)\u2010induced neuropilin\u20102 (NRP2) in rheumatoid arthritis (RA) and focused on its role in inflammation and disease progression and its potential as a therapeutic target in fibroblast\u2010like synoviocytes (FLS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Serum and synovial fluid (SF) samples were collected from healthy volunteers (serum, n\u00a0=\u00a030), patients with osteoarthritis (OA) (SF, n\u00a0=\u00a020), and patients with RA (serum, n\u00a0=\u00a076; SF, n\u00a0=\u00a021) for NRP2 quantification. Synovial tissues from patients with OA (n\u00a0=\u00a06) and RA (n\u00a0=\u00a06) were obtained to analyze NRP2 expression and its clinical relevance. Systemic or conditional NRP2 knockout mice were generated, and disease severity was evaluated in serum\u2013transfer\u2010induced arthritis (STIA) models. RA\u2010FLS were transfected with NRP2\u2010specific small interfering RNA to assess the effects on proliferation, apoptosis, and pro\u2010inflammatory cytokine secretion. Chromatin immunoprecipitation sequencing (ChIP\u2010seq) was performed to identify p65\u2010binding sites in the NRP2 locus.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      NRP2 levels in RA serum (n\u00a0=\u00a076) were elevated and correlated with disease activity. TNF up\u2010regulated NRP2 expression in FLS via the transcription factor p65, and elevated NRP2 in turn, amplified local inflammation and tissue damage by increasing FLS proliferation and promoting the release of cytokines, chemokines, and matrix metalloproteinases (MMPs). Both systemic and conditional knockout of NRP2 alleviated joint inflammation and damage in STIA models. The inflammatory regulation mediated by NRP2 was derived primarily from \u03b1\n                      <jats:sup>+<\/jats:sup>\n                      THY1\n                      <jats:sup>+<\/jats:sup>\n                      subset within the synovial sublining layer.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>TNF\u2010induced NRP2 drives inflammatory persistence in RA and serves as a promising diagnostic biomarker. Targeting the TNF\u2010p65\u2010NRP2 axis in FLS may offer a novel strategy for mitigating arthritis progression.<\/jats:p>\n                    <jats:p>\n                      <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                        <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/art70028-gra-0001-m.png\">\n                          <jats:alt-text>image<\/jats:alt-text>\n                        <\/jats:graphic>\n                      <\/jats:boxed-text>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.70028","type":"journal-article","created":{"date-parts":[[2025,12,26]],"date-time":"2025-12-26T09:36:23Z","timestamp":1766741783000},"page":"1062-1075","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Tumor Necrosis Factor\u2013Induced Neuropilin\u20102 in Fibroblast\u2010Like Synoviocytes Exacerbates Rheumatoid Arthritis"],"prefix":"10.1002","volume":"78","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5371-3440","authenticated-orcid":false,"given":"Ke","family":"Jin","sequence":"first","affiliation":[{"name":"Department of Rheumatology and Immunology, Laboratory of Human Diseases and Immunotherapies, Frontiers Science Center for Disease\u2010related Molecular Network West China Hospital, Sichuan University  Chengdu China"},{"name":"Institute of Immunology and Inflammation, West China Hospital, Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjing","family":"Ran","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Laboratory of Human Diseases and Immunotherapies, Frontiers Science Center for Disease\u2010related Molecular Network West China Hospital, Sichuan University  Chengdu China"},{"name":"Institute of Immunology and Inflammation, West China Hospital, Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxin","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Laboratory of Human Diseases and Immunotherapies, Frontiers Science Center for Disease\u2010related Molecular Network West China Hospital, Sichuan University  Chengdu China"},{"name":"Institute of Immunology and Inflammation, West China Hospital, Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyong","family":"Miao","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Laboratory of Human Diseases and Immunotherapies, Frontiers Science Center for Disease\u2010related Molecular Network West China Hospital, Sichuan University  Chengdu China"},{"name":"Institute of Immunology and Inflammation, West China Hospital, Sichuan University  Chengdu 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