{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T12:40:36Z","timestamp":1787229636504,"version":"build-2736575974"},"reference-count":50,"publisher":"BMJ","issue":"3","license":[{"start":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T00:00:00Z","timestamp":1758153600000},"content-version":"unspecified","delay-in-days":79,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/3.0\/igo\/"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["RMD Open"],"accepted":{"date-parts":[[2025,8,4]]},"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>Psoriatic arthritis (PsA) is an IL-23\/IL-17\/TNF-driven inflammatory arthritis, commonly accompanied by vitamin D deficiency. Here, we investigate the interaction between PsA synovial fibroblasts (SFs) and human memory CCR6+Th17 (hmemCCR6+Th17) cells and evaluate the therapeutic effects of TNF\u03b1 and\/or IL-17A inhibitors, and the adjunctive therapy potential of 1,25-dihydroxyvitamin D3 (1,25(OH)<jats:sub>2<\/jats:sub>D<jats:sub>3<\/jats:sub>).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>SF derived from PsA biopsies were co-cultured with hmemCCR6+Th17 cells to construct a PsA SF activation model. SF phenotypes were analysed by flow cytometry. Treatments included adalimumab (anti-TNF\u03b1), secukinumab (anti-IL-17A), and\/or 1,25(OH)<jats:sub>2<\/jats:sub>D<jats:sub>3<\/jats:sub>, applied alone or in combination. A transwell system was used to assess treatment effects on SF and hmemCCR6+Th17 cells. Cytokines and matrix metalloproteinases (MMPs) were quantified by ELISA.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>PsA SF were composed of heterogeneous subpopulations and constructed a pro-inflammatory feedback loop with hmemCCR6+Th17 cells. Anti-TNF\u03b1 and\/or anti-IL-17A significantly suppressed proinflammatory cytokines and tissue-destructive mediators in the PsA SF activation model, but showed limited effect on IL-22 and IFN\u03b3. Adding 1,25(OH)<jats:sub>2<\/jats:sub>D<jats:sub>3<\/jats:sub> to anti-TNF\u03b1 treatment effectively overcame the limitations of single anti-TNF\u03b1 in suppressing Th17 cytokines, while significantly enhancing the inhibition of IL-6, IL-8 and MMPs. In addition, 1,25(OH)<jats:sub>2<\/jats:sub>D<jats:sub>3<\/jats:sub> promoted the production of IL-10.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>TNF\u03b1 or IL-17A inhibition alone does not completely inhibit the proinflammatory loop between hmemCCR6+Th17 cells and PsA SF, although the combination shows additive effect on suppressing proinflammatory and tissue-destructive mediators. Importantly, 1,25(OH)<jats:sub>2<\/jats:sub>D<jats:sub>3<\/jats:sub> plays a complementary role in the treatment of this proinflammatory loop alongside anti-TNF\u03b1 therapy and significantly induces IL-10. Clinical PsA studies are needed to explore the additional therapeutic potential of this combination.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/rmdopen-2025-005547","type":"journal-article","created":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T05:35:12Z","timestamp":1758260112000},"page":"e005547","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":2,"title":["Active vitamin D acts in vitro as an adjuvant to anti-TNF\u03b1 treatment in a psoriatic synovial fibroblast activation model by modulating human Th17 activity"],"prefix":"10.1136","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-9962-7704","authenticated-orcid":false,"given":"Yi","family":"He","sequence":"first","affiliation":[{"name":"Rheumatology, Erasmus MC, Rotterdam, The Netherlands"},{"name":"EULAR Center of Excellence for Rheumatology Research, Erasmus MC, Rotterdam, The 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Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Radjesh","family":"Bisoendial","sequence":"additional","affiliation":[{"name":"Rheumatology and Clinical Immunology, Maasstad Hospital, Rotterdam, The Netherlands"},{"name":"Immunology, Erasmus MC, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik","family":"Lubberts","sequence":"additional","affiliation":[{"name":"Rheumatology, Erasmus MC, Rotterdam, The Netherlands"},{"name":"EULAR Center of Excellence for Rheumatology Research, Erasmus MC, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2025,9,18]]},"reference":[{"key":"2025091822350774000_11.3.e005547.1","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1038\/s41572-021-00293-y","article-title":"Psoriatic arthritis","volume":"7","author":"FitzGerald","year":"2021","journal-title":"Nat Rev Dis 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