{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T22:43:28Z","timestamp":1790808208581,"version":"4.1.0"},"reference-count":46,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2022,5,9]],"date-time":"2022-05-09T00:00:00Z","timestamp":1652054400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100008319","name":"Fondation Arthritis","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008319","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2022,6]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To characterize the role of interleukin\u20101\u03b2 (IL\u20101\u03b2) and microvascular endothelial cells (MVECs) in the generation of alternatively activated macrophages in the skin, and to explore their role in the development of skin fibrosis in patients with systemic sclerosis (SSc; scleroderma).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Conditioned medium prepared with MVECs purified from the skin of healthy donors and the skin of SSc patients was used to generate monocyte\u2010derived macrophages. Flow cytometry, multiplex protein assessment, real\u2010time quantitative polymerase chain reaction, and tissue immunofluorescence were used to characterize MVEC\u2010induced polarization of alternatively activated macrophages. Coculture experiments were conducted to assess the role of MVEC\u2010induced alternatively activated macrophages in fibroblast activation. Alternatively activated macrophages were characterized in the skin of healthy donors and SSc patients using multiparametric immunofluorescence and multiplex immunostaining for gene expression. Based on our in vitro data, we defined a supervised macrophage gene signature score to assess correlation between the macrophage score and clinical features in patients with SSc, using the Spearman's test.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      IL\u20101\u03b2\u2013activated MVECs from SSc patients induced monocytes to differentiate into DC\u2010SIGN+ alternatively activated macrophages producing high levels of CCL18, CCL2, and CXCL8 but low levels of IL\u201010. DC\u2010SIGN+ alternatively activated macrophages showed significant enhancing effects in promoting the production of proinflammatory fibroblasts and were found to be enriched in perivascular regions of the skin of SSc patients who had a high fibrosis severity score. A novel skin transcriptomic macrophage signature, defined from our in vitro findings, correlated with the extent of skin fibrosis (Spearman's r = 0.6,\n                      <jats:italic>P<\/jats:italic>\n                      = 0.0018) and was associated with early disease manifestations and lung involvement in patients with SSc.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our findings shed new light on the vicious circle implicating unabated IL\u20101\u03b2 secretion, MVEC activation, and the generation of DC\u2010SIGN+ alternatively activated macrophages in the development of skin fibrosis in patients with SSc.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.42061","type":"journal-article","created":{"date-parts":[[2021,12,28]],"date-time":"2021-12-28T07:15:04Z","timestamp":1640675704000},"page":"1013-1026","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Interleukin\u20101\u03b2\u2013Activated Microvascular Endothelial Cells Promote DC\u2010SIGN\u2013Positive Alternatively Activated Macrophages as a Mechanism of Skin Fibrosis in Systemic Sclerosis"],"prefix":"10.1002","volume":"74","author":[{"given":"Pa\u00f4line","family":"Laurent","sequence":"first","affiliation":[{"name":"Immunoconcept, CNRS UMR 5164, Bordeaux University  Bordeaux France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joelle","family":"Lapoirie","sequence":"additional","affiliation":[{"name":"University Hospital Centre Bordeaux  Bordeaux 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