{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,6]],"date-time":"2026-09-06T23:08:28Z","timestamp":1788736108975,"version":"build-2803163510"},"reference-count":43,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,6]],"date-time":"2026-09-06T00:00:00Z","timestamp":1788652800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,6]],"date-time":"2026-09-06T00:00:00Z","timestamp":1788652800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["PO1 AI 179405"],"award-info":[{"award-number":["PO1 AI 179405"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"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>Podocyte injury drives proteinuria and disease progression in lupus nephritis (LN), yet the mechanisms underlying podocyte dysfunction remain incompletely understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Sera samples from 39 patients with systemic lupus erythematosus, including 15 patients with LN and 13 healthy controls, were collected. Levels of interleukin\u201012 (IL\u201012) were measured by enzyme\u2010linked immunosorbent assay. Expression of IL\u201012 receptors (IL\u201012Rs) was assessed by immunofluorescence staining. Immortalized human podocyte cell line was used for in vitro study. The podocyte conditional knockout of\n                      <jats:italic>Il12rb1<\/jats:italic>\n                      mice including B6.\n                      <jats:italic>Il12rb1<\/jats:italic>\n                      <jats:sup>fl\/fl<\/jats:sup>\n                      <jats:italic>Nphs2<\/jats:italic>\n                      <jats:sup>cre<\/jats:sup>\n                      mice and B6.lpr.\n                      <jats:italic>Il12rb1<\/jats:italic>\n                      <jats:sup>fl\/fl<\/jats:sup>\n                      <jats:italic>Nphs2<\/jats:italic>\n                      <jats:sup>cre<\/jats:sup>\n                      mice was generated. Accelerated lupus model and nephrotoxic nephritis model were induced. B6.\n                      <jats:italic>Il12rb1<\/jats:italic>\n                      <jats:sup>fl\/fl<\/jats:sup>\n                      and B6.lpr.\n                      <jats:italic>Il12rb1<\/jats:italic>\n                      <jats:sup>fl\/fl<\/jats:sup>\n                      mice were used as control.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Serum levels of IL\u201012 were elevated in patients with LN (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.006) and in mice who were lupus prone (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.041). Expression of the IL\u201012R was increased in podocytes in both human and murine LN. IL\u201012 stimulation induced the phosphorylation of calcium\/calmodulin\u2010dependent protein kinase 4 and STAT4, causing mitochondrial dysfunction and increased reactive oxygen species accumulation, leading to accelerated podocyte senescence, senescence\u2010associated secretory phenotype, and cytoskeleton disorganization. Podocyte\u2010specific deletion of\n                      <jats:italic>Il12rb1<\/jats:italic>\n                      attenuated podocyte senescence, ameliorated glomerular injury, and reduced proteinuria in both mice who were lupus prone and normal mice injected with a nephrotoxic serum.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our findings identify IL\u201012 signaling as an important mediator of podocyte senescence in LN and suggest that targeting the IL\u201012\u2013IL\u201012R axis may offer future therapeutic approaches to preserve podocytes and attenuate LN.<\/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\/art70305-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.70305","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T11:39:55Z","timestamp":1787571595000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Interleukin\u201012 Signaling Promotes Podocyte Senescence in Lupus Nephritis"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1822-8017","authenticated-orcid":false,"given":"Chaohuan","family":"Guo","sequence":"first","affiliation":[{"name":"Department of Medicine, Beth Israel Deaconess Medical Center Harvard Medical School  Boston 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