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Among the most severe manifestations of SLE is lupus nephritis (LN), which causes particularly high morbidity. Recently, we identified amphiregulin (AREG), an epidermal growth factor receptor ligand, as a key mediator of LN via downregulation of pathogenic CD4\n                    <jats:sup>+<\/jats:sup>\n                    T-cell responses. In human LN, AREG is mainly produced by regulatory T cells (Tregs) and monocytes\/macrophages (M\/M). Since AREG\u00b4s functions have been shown to vary considerably depending on the source, we aimed to clarify the cell-type-specific roles of AREG using the pristane model of LN. Conditional knockout mice lacking Treg- but not M\/M-derived AREG showed worse LN outcome at 12 and 15 months with increased glomerular cell proliferation, apoptosis and renal tissue fibrosis. Interestingly, immune responses were not relevantly affected by the lack of AREG from either leukocyte source, indicating a different mechanism. In this respect, in vitro studies demonstrated improved wound healing of murine mesangium and tubulus cells and enhanced regeneration and sprouting of human glomerular endothelial cells after incubation with recombinant AREG. These findings underscore the importance of Treg-derived AREG in tissue regeneration and protection from fibrosis in LN, highlighting AREG as a potential therapeutic target.\n                  <\/jats:p>","DOI":"10.1038\/s41598-025-91636-2","type":"journal-article","created":{"date-parts":[[2025,3,5]],"date-time":"2025-03-05T12:59:25Z","timestamp":1741179565000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Treg derived Amphiregulin protects from murine lupus nephritis via tissue reparative effects"],"prefix":"10.1038","volume":"15","author":[{"given":"Laura-Isabell","family":"Ehnold","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Melderis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Hagenstein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias T.","family":"Warkotsch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viona","family":"Laas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederic C.","family":"Feindt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias B.","family":"Huber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Grahammer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver M.","family":"Steinmetz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,3,5]]},"reference":[{"key":"91636_CR1","doi-asserted-by":"publisher","unstructured":"Kaul, A. et al. 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