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Transl. Med."],"published-print":{"date-parts":[[2026,6,24]]},"abstract":"<jats:p>\n                    In chronic inflammatory diseases, maladaptive tissue remodeling is driven by a complex interplay of resident cells, immune infiltrates, and the extracellular matrix. In the autoimmune disorder rheumatoid arthritis (RA), synovial tissue undergoes massive expansion to form an invasive pannus that drives the erosion of cartilage and bone. The mechanisms mediating this aggressive growth are incompletely defined. Using spatial transcriptomic profiling of patient tissue, we detected an abundance of proliferating fibroblasts near the synovial tissue lining surface and adjacent to macrophages expressing high levels of\n                    <jats:italic toggle=\"yes\">secreted phosophoprotein-1<\/jats:italic>\n                    (encoding osteopontin;\n                    <jats:italic toggle=\"yes\">SPP1<\/jats:italic>\n                    <jats:sup>hi<\/jats:sup>\n                    macrophages). These synovial lining regions were also distinctly marked by deposits of the clot-forming protein fibrin. Although the\n                    <jats:italic toggle=\"yes\">SPP1<\/jats:italic>\n                    <jats:sup>hi<\/jats:sup>\n                    macrophages phenotypically resembled the profibrotic macrophages that drive lung and liver fibrosis, these niches were devoid of the dense highly ordered collagen that marks fibrosis. Functionally, we found that\n                    <jats:italic toggle=\"yes\">SPP1<\/jats:italic>\n                    <jats:sup>hi<\/jats:sup>\n                    macrophages degraded and phagocytosed fibrin matrices and promoted fibroblast proliferation. Given that fibrin provides transient matrices for de novo tissue generation in the context of wound healing, these data support a model of hyperplastic tissue outgrowth involving\n                    <jats:italic toggle=\"yes\">SPP1<\/jats:italic>\n                    <jats:sup>hi<\/jats:sup>\n                    macrophages, fibroblasts, and fibrin matrices adhered to the exterior synovial tissue surface. Whereas current RA therapies primarily aim to dampen proinflammatory responses, our findings provide the rationale for targeting progenerative pathways and\n                    <jats:italic toggle=\"yes\">SPP1<\/jats:italic>\n                    <jats:sup>hi<\/jats:sup>\n                    macrophages.\n                  <\/jats:p>","DOI":"10.1126\/scitranslmed.aed3087","type":"journal-article","created":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T17:58:11Z","timestamp":1782323891000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":3,"title":["<i>SPP1<\/i>\n                    <sup>hi<\/sup>\n                    macrophages in fibrin niches promote hyperplastic tissue remodeling in rheumatoid arthritis synovium"],"prefix":"10.1126","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2609-4028","authenticated-orcid":true,"given":"Ian","family":"Mantel","sequence":"first","affiliation":[{"name":"Immunology and Microbial Pathogenesis Graduate Program, Weill Cornell Graduate School, New York, NY 10065, USA."},{"name":"HSS Research Institute, Hospital for Special Surgery, New York, NY 10021, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-0585-7984","authenticated-orcid":true,"given":"Haoxuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Tri-Institutional Training Program in Computational Biology and Medicine, Weill Cornell Medicine, New York, NY 10065, USA."},{"name":"Computational &amp; 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