{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T14:29:44Z","timestamp":1788532184436,"version":"build-2803163510"},"reference-count":35,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp;amp; Rheumatology"],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To determine whether down\u2010regulation of the transcription factor Fli1 in myeloid cells, previously implicated in profibrotic programming in systemic sclerosis (SSc), promotes cardiac fibrosis and dysfunction in SSc and to define the underlying mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Immunohistochemistry for Fli1 and galectin\u20103 (Gal\u20103) was performed on SSc and control cardiac tissue (n\u00a0=\u00a06\u20137). Circulating monocytes were analyzed for Gal\u20103 protein and messenger RNA (mRNA) levels. Cardiac fibrosis and function were evaluated in young and aged myeloid\u2010specific Fli1 knockout mice (Lyz2Cre\/Fli1\n                      <jats:sup>fl\/fl<\/jats:sup>\n                      ), by collagen staining and echocardiography. Co\u2010culture experiments using human macrophages and primary human cardiac fibroblasts, Fli1 and Gal\u20103 knockdown, recombinant human Gal\u20103, and rapamycin were used to dissect mTORC1\u2010dependent profibrotic signaling.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Fli1 expression was reduced (~6\u2010fold,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.0103), whereas Gal\u20103 was increased (~4\u2010fold,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.0031) in SSc myocardium compared with control. SSc monocytes expressed elevated Gal\u20103 protein (~2\u2010fold,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.0235) and mRNA levels (~1.7\u2010fold,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.0448). Lyz2Cre \/Fli1\n                      <jats:sup>fl\/fl<\/jats:sup>\n                      mice had increased myocardial collagen and diastolic dysfunction with elevated mitral E\/e\u2032 (23.79\u2009\u00b1\u20098.11 vs 18.76\u2009\u00b1\u20098.09,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.04) but preserved systolic function; in aged mice, fibrosis was further increased, and systolic function was also impaired (left ventricular ejection fraction 47.41\u2009\u00b1\u20095.07 vs 66.15\u2009\u00b1\u200911.49,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.0006). Mechanistically, Fli1 loss derepressed the\n                      <jats:italic>LGALS3<\/jats:italic>\n                      promoter, increasing Gal\u20103 in macrophages and activating mTORC1 in cardiac fibroblasts, and Gal\u20103 or mTORC1 inhibition blunted fibroblast activation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Fli1 deficiency in myeloid cells drives Gal\u20103\u2013dependent activation of mTORC1 in cardiac fibroblasts, promoting cardiac fibrosis and dysfunction in SSc. These findings identify a myeloid Fli1\u2013Gal\u20103\u2013mTORC1 axis as a central pathway in SSc\u2010associated cardiac fibrosis and a potential therapeutic target.<\/jats:p>\n                    <jats:p>\n                      <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                        <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/art70299-gra-0001-m.png\">\n                          <jats:alt-text>image<\/jats:alt-text>\n                        <\/jats:graphic>\n                      <\/jats:boxed-text>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.70299","type":"journal-article","created":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T06:26:12Z","timestamp":1788330372000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Down\u2010Regulated Fli1 in Scleroderma Myeloid Cells Contributes to Cardiac Fibrosis Via a Galectin\u20103\/\n                    <scp>mTOR<\/scp>\n                    Dependent Pathway"],"prefix":"10.1002","author":[{"given":"Fatima","family":"El Adili","sequence":"first","affiliation":[{"name":"Division of Rheumatology Boston University Chobanian &amp; Avedisian School of Medicine  Boston Massachusetts"},{"name":"Arthritis and Autoimmune Diseases Center Boston University Chobanian &amp; Avedisian School of Medicine  Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Knowledge M.","family":"Moyo","sequence":"additional","affiliation":[{"name":"Division of Rheumatology Boston University Chobanian &amp; Avedisian School of Medicine  Boston Massachusetts"},{"name":"Arthritis and Autoimmune Diseases Center Boston University Chobanian &amp; Avedisian School of Medicine  Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hung","family":"Vo","sequence":"additional","affiliation":[{"name":"Division of Rheumatology Boston University Chobanian &amp; Avedisian School of Medicine  Boston Massachusetts"},{"name":"Arthritis and Autoimmune Diseases Center Boston University Chobanian &amp; Avedisian School of Medicine  Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Kissin","sequence":"additional","affiliation":[{"name":"Arthritis and Autoimmune Diseases Center Boston University Chobanian &amp; Avedisian School of Medicine  Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-6372-2269","authenticated-orcid":false,"given":"Jerry","family":"Yang","sequence":"additional","affiliation":[{"name":"Arthritis and Autoimmune Diseases Center Boston University Chobanian &amp; Avedisian School of Medicine  Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehmed T.","family":"Dinc","sequence":"additional","affiliation":[{"name":"Division of Rheumatology Boston University Chobanian &amp; Avedisian School of Medicine  Boston Massachusetts"},{"name":"Arthritis and Autoimmune Diseases Center Boston University Chobanian &amp; Avedisian School of Medicine  Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey","family":"Browning","sequence":"additional","affiliation":[{"name":"Arthritis and Autoimmune Diseases Center Boston University Chobanian &amp; Avedisian School of Medicine  Boston Massachusetts"},{"name":"Department of Microbiology Boston University Chobanian &amp; 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