biostudies-literatureMeyer ABLRD VADepartment of Veteran’s AffairsInnovative Research Award from the Rheumatology Research FoundationNIAID NIH HHSMedical Research CouncilFoundation for the National Institutes of Health483-495https://www.ebi.ac.uk/biostudies/studies/S-EPMC10314955biostudies-literatureUnknown82(4)<h4>Objectives</h4>Syntenin-1, a novel endogenous ligand, was discovered to be enriched in rheumatoid arthritis (RA) specimens compared with osteoarthritis synovial fluid and normal synovial tissue (ST). However, the cellular origin, immunoregulation and molecular mechanism of syntenin-1 are undescribed in RA.<h4>Methods</h4>RA patient myeloid and lymphoid cells, as well as preclinical models, were used to investigate the impact of syntenin-1/syndecan-1 on the inflammatory and metabolic landscape.<h4>Results</h4>Syntenin-1 and syndecan-1 (SDC-1) co-localise on RA ST macrophages (MΦs) and endothelial cells. Intriguingly, blood syntenin-1 and ST SDC-1 transcriptome are linked to cyclic citrullinated peptide, erythrocyte sedimentation rate, ST thickness and bone erosion. Metabolic CD14<sup>+<Annals of the rheumatic diseasesSyntenin-1-mediated arthritogenicity is advanced by reprogramming RA metabolic macrophages and Th1 cells.PMC10314955MERIT Award BX002286G0800648R41 AI147697I01 BX002286NIH R01 AI167155R01 AI167155NIH R41 AI147697Lewis MUmar SJetanalin PShahrara SSweiss NVan Raemdonck KAl-Awqati MVolin MVZanotti BNijim WChang HJArami SPitzalis CSchett GMeyer ASienes REfalseSyntenin-1-mediated arthritogenicity is advanced by reprogramming RA metabolic macrophages and Th1 cells.<h4>Objectives</h4>Syntenin-1, a novel endogenous ligand, was discovered to be enriched in rheumatoid arthritis (RA) specimens compared with osteoarthritis synovial fluid and normal synovial tissue (ST). However, the cellular origin, immunoregulation and molecular mechanism of syntenin-1 are undescribed in RA.<h4>Methods</h4>RA patient myeloid and lymphoid cells, as well as preclinical models, were used to investigate the impact of syntenin-1/syndecan-1 on the inflammatory and metabolic landscape.<h4>Results</h4>Syntenin-1 and syndecan-1 (SDC-1) co-localise on RA ST macrophages (MΦs) and endothelial cells. Intriguingly, blood syntenin-1 and ST SDC-1 transcriptome are linked to cyclic citrullinated peptide, erythrocyte sedimentation rate, ST thickness and bone erosion. Metabolic CD14<sup>+<2023-01-01T00:00:00Z2023 Apr2025-04-04T19:58:08.039Z2025-04-04T19:58:08.039ZS-EPMC103149553659309110.1136/ard-2022-223284