{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T21:24:47Z","timestamp":1792013087129,"version":"4.4.0"},"reference-count":44,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T00:00:00Z","timestamp":1759708800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"the National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81971534"],"award-info":[{"award-number":["81971534"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"the National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82402096"],"award-info":[{"award-number":["82402096"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Shanghai Sailing Program","award":["24YF2725000"],"award-info":[{"award-number":["24YF2725000"]}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"crossref","award":["2024M762042"],"award-info":[{"award-number":["2024M762042"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Shanghai Pujiang Program","award":["24PJA073"],"award-info":[{"award-number":["24PJA073"]}]}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["IJMS"],"abstract":"<jats:p>Macrophages play a central role in joint inflammation and bone destruction in rheumatoid arthritis (RA). While activator protein-1 (AP-1) transcription factors have been implicated in RA pathogenesis, the specific roles of individual AP-1 members in regulating synovial macrophages remain unclear. To address this, two public single-cell transcriptomic datasets were first analyzed to profile synovial macrophages, and then to identify AP-1 family members and associated pathways via differential expression and gene set enrichment analyses. JUND, FOSL2, and FOSB were found to be highly enriched in the RA synovium, and a distinct CXCL3+FOSL2+ macrophage subset was identified, characterized by pro-inflammatory, metabolic, and differentiation-related pathways. Intercellular communication analysis further revealed that this CXCL3+FOSL2+ macrophage subset interacted with ACKR1+ endothelial cells within the synovial microenvironment. Validation in a large-cohort bulk transcriptomic dataset, together with functional assays using in vitro FOSL2 knockdown in U937 cell lines, further confirmed FOSL2\u2019s role in promoting macrophage-driven inflammation. Collectively, these findings indicate that CXCL3+FOSL2+ macrophages drive RA synovitis via the FOSL2\/AP-1 axis, highlighting a potential therapeutic target.<\/jats:p>","DOI":"10.3390\/ijms26199718","type":"journal-article","created":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T15:05:06Z","timestamp":1759763106000},"page":"9718","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Synovial CXCL3+FOSL2+ Macrophages Mediate Inflammation via FOSL2\/AP-1 in Rheumatoid Arthritis: A Single-Cell Transcriptome Analysis"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-3981-2595","authenticated-orcid":false,"given":"Yiwei","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200001, China"},{"name":"Department of Allergy, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinming","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200001, China"},{"name":"Department of Allergy, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-8983-4701","authenticated-orcid":false,"given":"Mengke","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5183-1029","authenticated-orcid":false,"given":"Xiaoxiang","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200001, China"},{"name":"Department of Allergy, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shan","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2023","DOI":"10.1016\/S0140-6736(16)30173-8","article-title":"Rheumatoid arthritis","volume":"388","author":"Smolen","year":"2016","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1056\/NEJMra2103726","article-title":"Rheumatoid Arthritis\u2014Common Origins, Divergent Mechanisms","volume":"388","author":"Gravallese","year":"2023","journal-title":"N. 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