{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T13:46:52Z","timestamp":1790344012771,"version":"4.1.0"},"reference-count":66,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2019,7,1]],"date-time":"2019-07-01T00:00:00Z","timestamp":1561939200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The signals that control endothelial plasticity in inflamed tissues have only been partially characterized. For example, it has been shown that inadequate vasculogenesis in systemic sclerosis (SSc) has been associated with an endothelial defect. We used a genetic lineage tracing model to investigate whether endothelial cells die or change phenotypically after fibrosis induction and whether signals released by cells of the innate immune system and in the blood of patients influence their commitment. We observed that in the lineage-tracing transgenic mice Cdh5-CreERT2::R26R-EYFP, endothelial-derived cells (EdCs) underwent fibrosis after treatment with bleomycin, and EdCs retrieved from the lung showed expression of endothelial-to-mesenchymal transition (EndoMT) markers. Liposome-encapsulated clodronate was used to assess macrophage impact on EdCs. Clodronate treatment affected the number of alternatively activated macrophages in the lung, with upregulated expression of EndoMT markers in lung EdCs. Endothelial fate and function were investigated in vitro upon challenge with serum signals from SSc patients or released by activated macrophages. Sera of SSc patients with anti-Scl70 Abs, at higher risk of visceral organ fibrosis, induced EndoMT and jeopardized endothelial function. In conclusion, EdCs in SSc might be defective because of commitment to a mesenchymal fate, which is sustained by soluble signals in the patient\u2019s blood. Macrophages contribute to preserve the endothelial identity of precursor cells. Altered macrophage-dependent plasticity of EdCs could contribute to link vasculopathy with fibrosis.<\/jats:p>","DOI":"10.4049\/jimmunol.1800883","type":"journal-article","created":{"date-parts":[[2019,5,24]],"date-time":"2019-05-24T20:14:08Z","timestamp":1558728848000},"page":"247-258","source":"Crossref","is-referenced-by-count":15,"title":["Macrophages Guard Endothelial Lineage by Hindering Endothelial-to-Mesenchymal Transition: Implications for the Pathogenesis of Systemic Sclerosis"],"prefix":"10.1093","volume":"203","author":[{"given":"Pier Andrea","family":"Nicolosi","sequence":"first","affiliation":[{"name":"School of Medicine and Surgery, University of Milano-Bicocca , 20900 Monza ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrico","family":"Tombetti","sequence":"additional","affiliation":[{"name":"Division of Immunology, Transplantation and Infectious Disease, IRCCS San Raffaele Scientific Institute , 20132 Milan ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3889-456X","authenticated-orcid":false,"given":"Anna","family":"Giovenzana","sequence":"additional","affiliation":[{"name":"School of Medicine and Surgery, University of Milano-Bicocca , 20900 Monza ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleonora","family":"Don\u00e8","sequence":"additional","affiliation":[{"name":"School of Medicine and Surgery, University of Milano-Bicocca , 20900 Monza ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleonora","family":"Pulcinelli","sequence":"additional","affiliation":[{"name":"School of Medicine and Surgery, University of Milano-Bicocca , 20900 Monza ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0791-5951","authenticated-orcid":false,"given":"Raffaella","family":"Meneveri","sequence":"additional","affiliation":[{"name":"School of Medicine and Surgery, University of Milano-Bicocca , 20900 Monza ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Tirone","sequence":"additional","affiliation":[{"name":"School of Medicine and Surgery, University of Milano-Bicocca , 20900 Monza ,","place":["Italy"]},{"name":"Division of Genetics and Cell Biology, IRCCS San Raffaele Scientific Institute , 20132 Milan ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3931-0412","authenticated-orcid":false,"given":"Norma","family":"Maugeri","sequence":"additional","affiliation":[{"name":"Division of Immunology, Transplantation and Infectious Disease, IRCCS San Raffaele Scientific Institute , 20132 Milan ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrizia","family":"Rovere-Querini","sequence":"additional","affiliation":[{"name":"Division of Immunology, Transplantation and Infectious Disease, IRCCS San Raffaele Scientific Institute , 20132 Milan ,","place":["Italy"]},{"name":"Universit\u00e0 Vita-Salute San Raffaele , 20132 Milan ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelo A","family":"Manfredi","sequence":"additional","affiliation":[{"name":"Division of Immunology, Transplantation and Infectious Disease, IRCCS San Raffaele Scientific Institute , 20132 Milan ,","place":["Italy"]},{"name":"Universit\u00e0 Vita-Salute San Raffaele , 20132 Milan ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1753-5346","authenticated-orcid":false,"given":"Silvia","family":"Brunelli","sequence":"additional","affiliation":[{"name":"School of Medicine and Surgery, University of Milano-Bicocca , 20900 Monza ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,7,1]]},"reference":[{"key":"2025030418132825400_r1","doi-asserted-by":"crossref","first-page":"1989","DOI":"10.1056\/NEJMra0806188","article-title":"Scleroderma","volume":"360","author":"Gabrielli","year":"2009","journal-title":"N. 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