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Effective anti\u2010fibrotic treatments are scarce, except for orbital decompression surgery involving orbital adipose tissue (OAT) removal, due to high rates of drug resistance following hyperthyroidism treatment and the lack of suitable mouse models. Understanding the mechanisms behind fibrotic remodeling of OAT could aid mouse model development and identify novel therapies. In the present study, stromal vascular fraction cells of OAT from patients with inactive\u2010stage TED, characterized by pronounced fibrosis, are analyzed at single\u2010cell resolution. platelet\u2010derived growth factor receptor (PDGFR)\u03b1\n                    <jats:sup>+<\/jats:sup>\n                    dipeptidyl peptidase (DPP)4\n                    <jats:sup>+<\/jats:sup>\n                    fibroblasts exhibiting progenitor characteristics and fibrotic potential at the transcriptional level are identified. PDGFR\u03b1\n                    <jats:sup>+<\/jats:sup>\n                    DPP4\n                    <jats:sup>+<\/jats:sup>\n                    fibroblasts showed the strongest interactions with macrophages, particularly M2 macrophages, which are enriched and topographically localized within the fibrotic area. Moreover, M2 macrophages promoted extracellular matrix production in PDGFR\u03b1\n                    <jats:sup>+<\/jats:sup>\n                    DPP4\n                    <jats:sup>+<\/jats:sup>\n                    cells via the Growth arrest specific (GAS)6\u2010AXL Receptor Tyrosine Kinase (AXL) signaling pathway. Using a specific AXL inhibitor or AXL knockdown, fibrosis is substantially reduced in PDGFR\u03b1\n                    <jats:sup>+<\/jats:sup>\n                    DPP4\n                    <jats:sup>+<\/jats:sup>\n                    fibroblasts in vitro, and in patient cell\u2010derived orthotopic xenograft models established via GAS6. By identifying pro\u2010fibrotic intercellular networks in OAT, these findings establish a rapid and repeatable mouse model of TED fibrosis and propose the GAS6\u2010AXL axis as a potential therapeutic target for TED.\n                  <\/jats:p>","DOI":"10.1002\/advs.202511404","type":"journal-article","created":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T09:59:17Z","timestamp":1759139957000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["PDGFR\u03b1\n                    <sup>+<\/sup>\n                    DPP4\n                    <sup>+<\/sup>\n                    Fibroblasts\u2010Macrophage Crosstalk Induces Orbital Fibrosis in Treatment\u2010Resistant Thyroid Eye Disease via the GAS6\u2010AXL Pathway"],"prefix":"10.1002","volume":"12","author":[{"given":"Lu","family":"Cheng","sequence":"first","affiliation":[{"name":"National Clinical Research Center for Eye Diseases Shanghai General Hospital 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