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However, how cell interactions within CNs shape the inflammatory microenvironment in RA remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Here, we used imaging mass cytometry and single\u2010cell RNA sequencing to dissect the CNs within RA synovium, uncovering critical cell\u2010cell interactions and evaluating whether disrupting interaction signals could alleviate disease severity in a collagen\u2010induced arthritis (CIA) mouse model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Our findings revealed that CNs enriched with fibroblast\u2010like synoviocytes (FLSs) and immune cells, particularly FLSs and macrophages, were more frequent in RA synovium compared with osteoarthritis. Further single\u2010cell RNA sequencing analysis showed that FLSs specifically up\u2010regulated complement C3 whereas macrophages displayed high levels of the C3 receptor, C3aR1. Interestingly, C3a derived from the FLS\u2010enhanced type I interferon response in macrophages, and the blockade of the C3a\u2010C3aR1 signaling reduced the secretion of interferon \u03b2 in macrophages, thereby affecting FLS activation. Additionally, inhibition of C3a\u2010C3aR1 signaling attenuated the severity of CIA mice with decreased immune cell infiltration, reduced FLS activation, and lessened bone destruction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our study suggests that FLS promotes synovial inflammation via interaction with macrophages through a C3a\u2010C3aR1 signaling\u2010mediated positive feedback regulation. Thus, targeting C3a\u2010C3aR1 signaling might provide a new therapeutic strategy for RA.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.43319","type":"journal-article","created":{"date-parts":[[2025,7,14]],"date-time":"2025-07-14T09:39:34Z","timestamp":1752485974000},"page":"1697-1712","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["C3a\u2013\n                    <scp>C3aR1<\/scp>\n                    \u2013Mediated Interactions Between Fibroblast\u2013Like Synoviocytes and Macrophages Promote the Progression of Rheumatoid Arthritis"],"prefix":"10.1002","volume":"77","author":[{"given":"Minglong","family":"Cai","sequence":"first","affiliation":[{"name":"Departments of Rheumatology and Immunology The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China  Hefei Anhui China"},{"name":"Department of Dermatology The First Affiliated 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