{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T13:55:36Z","timestamp":1787320536312,"version":"build-2736575974"},"reference-count":23,"publisher":"S. Karger AG","issue":"6","license":[{"start":{"date-parts":[[2022,1,1]],"date-time":"2022-01-01T00:00:00Z","timestamp":1640995200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2022,1,1]],"date-time":"2022-01-01T00:00:00Z","timestamp":1640995200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Innate Immun"],"published-print":{"date-parts":[[2022]]},"abstract":"<jats:p>Growth and differentiation factor 15 (GDF15), a divergent member of the transforming growth factor-\u03b2 superfamily, has been associated with acute and chronic inflammatory conditions including autoimmune disease, i.e., type I diabetes and rheumatoid arthritis. Still, its role in systemic autoimmune disease remains elusive. Thus, we studied GDF15-deficient animals in Fas-receptor intact (C57BL\/6) or deficient (C57BL\/6&lt;sup&gt;&lt;i&gt;lpr\/lpr&lt;\/i&gt;&lt;\/sup&gt;) backgrounds. Further, lupus nephritis (LN) microdissected kidney biopsy specimens were analyzed to assess the involvement of GDF15 in human disease. GDF15-deficiency in lupus-prone mice promoted lymphoproliferation, T-, B- and plasma cell-expansion, a type I interferon signature, and increased serum levels of anti-DNA autoantibodies. Accelerated systemic inflammation was found in association with a relatively mild renal phenotype. Splenocytes of phenotypically overall-normal &lt;i&gt;Gdf15\u2212\/\u2212&lt;\/i&gt; C57BL\/6 and lupus-prone C57BL\/6&lt;sup&gt;&lt;i&gt;lpr\/lpr&lt;\/i&gt;&lt;\/sup&gt; mice displayed increased in vitro lymphoproliferative responses or interferon-dependent transcription factor induction in response to the toll-like-receptor (TLR)-9 ligand CpG, or the TLR-7 ligand Imiquimod, respectively. In human LN, GDF15 expression was downregulated whereas type I interferon expression was upregulated in glomerular- and tubular-compartments versus living donor controls. These findings demonstrate that GDF15 regulates lupus-like autoimmunity by suppressing lymphocyte-proliferation and -activation. Further, the data indicate a negative regulatory role for GDF15 on TLR-7 and -9 driven type I interferon signaling in effector cells of the innate immune system.<\/jats:p>","DOI":"10.1159\/000523991","type":"journal-article","created":{"date-parts":[[2022,4,20]],"date-time":"2022-04-20T17:00:31Z","timestamp":1650474031000},"page":"673-689","source":"Crossref","is-referenced-by-count":24,"title":["GDF15 Suppresses Lymphoproliferation and Humoral Autoimmunity in a Murine Model of Systemic Lupus Erythematosus"],"prefix":"10.1159","volume":"14","author":[{"given":"Georg","family":"Lorenz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Ribeiro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekatharina","family":"von 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