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Institute for Translational AngioCardioScience"},{"name":"Early Career Investigator","award":["7.11442HIEC2401"],"award-info":[{"award-number":["7.11442HIEC2401"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Cardiovascular disease (CVD) is the leading cause of mortality in chronic kidney disease (CKD). While CKD is known to give rise to systemic inflammation, its inciting factors remain poorly defined. Oxalate, long implicated in rare genetic kidney disorders, accumulates with decreased kidney function and has emerged as a driver of inflammation and independent risk factor for CVD. Here, we investigate the immunological mechanisms linking oxalate nephropathy to systemic inflammation, cardiac damage and kidney injury.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>Oxalate nephropathy was induced in C57BL6\/N mice through an oxalate-enriched diet. Oxalate induced systemic immune activation, renal fibrosis, and adverse cardiac remodelling, including pulmonary congestion with systolic and diastolic dysfunction. Flow cytometry analysis identified interleukin (IL)-17A as a dominant inflammatory effector, with expansion of Th17 and Th17-like Treg in the kidney, intestine, and spleen. Bulk mRNA sequencing confirmed these findings in kidney and heart. In line, plasma IL-17A was increased in oxalate-fed mice. Confirming the oxalate-IL-17A relationship, plasma IL-17A was elevated in patients with primary hyperoxaluria. Gut microbiome analysis by 16S amplicon sequencing showed only mild oxalate-induced alterations in mice. However, soluble oxalate directly enhanced Th17 polarization and disrupted mitochondrial respiration in vitro. In vivo, antibody-mediated IL-17A blockade improved kidney function, cardiac fibrosis, reduced neutrophil infiltration, and partially restored cardiac function in oxalate-fed mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our study identifies oxalate as a systemic immunometabolic stressor and IL-17A as a central mediator of oxalate-induced cardiorenal injury. These findings establish the oxalate-IL-17A axis as a mechanistic link between CKD and CVD and suggest IL-17A inhibition as a potential therapeutic strategy to reduce cardiovascular damage in CKD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/cvr\/cvag158","type":"journal-article","created":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T11:47:13Z","timestamp":1783424833000},"page":"1851-1864","source":"Crossref","is-referenced-by-count":1,"title":["Interleukin-17A mediates cardiorenal injury in oxalate nephropathy"],"prefix":"10.1093","volume":"122","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-5793-0249","authenticated-orcid":false,"given":"Moritz I","family":"Wimmer","sequence":"first","affiliation":[{"name":"Experimental and Clinical Research Center (ECRC), a cooperation of Charite\u0301 \u2013 Universita\u0308tsmedizin Berlin and Max Delbr\u00fcck Center for Molecular Medicine , Berlin ,","place":["Germany"]},{"name":"Max-Delbru\u0308ck-Center for Molecular Medicine in the Helmholtz Association , Berlin ,","place":["Germany"]},{"name":"DZHK (German Centre for Cardiovascular Research), partner site Berlin , Berlin ,","place":["Germany"]},{"name":"Department of Nephrology and Medical Intensive Care, Charite\u0301 \u2013 Universita\u0308tsmedizin Berlin, corporate member of Freie Universita\u0308t Berlin and Humboldt-Universita\u0308t zu Berlin , Berlin ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7886-2784","authenticated-orcid":false,"given":"Martin","family":"Reichel","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Medical Intensive Care, Charite\u0301 \u2013 Universita\u0308tsmedizin Berlin, corporate member of Freie Universita\u0308t Berlin and Humboldt-Universita\u0308t zu Berlin , Berlin ,","place":["Germany"]},{"name":"Max Rubner Center for Cardiovascular Metabolic Renal Research, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin , Berlin ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0786-2239","authenticated-orcid":false,"given":"Arne","family":"Thiele","sequence":"additional","affiliation":[{"name":"Experimental and Clinical Research Center (ECRC), a cooperation of Charite\u0301 \u2013 Universita\u0308tsmedizin Berlin and Max Delbr\u00fcck Center for Molecular Medicine , Berlin ,","place":["Germany"]},{"name":"Max-Delbru\u0308ck-Center for Molecular Medicine in the Helmholtz Association , Berlin ,","place":["Germany"]},{"name":"DZHK (German Centre for Cardiovascular Research), partner site Berlin , Berlin ,","place":["Germany"]},{"name":"Department of Nephrology and Medical Intensive Care, Charite\u0301 \u2013 Universita\u0308tsmedizin Berlin, corporate member of Freie Universita\u0308t Berlin and Humboldt-Universita\u0308t zu Berlin , Berlin ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1724-0559","authenticated-orcid":false,"given":"Alex","family":"Yarritu","sequence":"additional","affiliation":[{"name":"Experimental and Clinical Research Center (ECRC), a cooperation of Charite\u0301 \u2013 Universita\u0308tsmedizin Berlin and Max Delbr\u00fcck Center for Molecular Medicine , Berlin ,","place":["Germany"]},{"name":"Max-Delbru\u0308ck-Center for Molecular Medicine in the Helmholtz Association , Berlin ,","place":["Germany"]},{"name":"DZHK (German Centre for Cardiovascular Research), partner site Berlin , Berlin ,","place":["Germany"]},{"name":"Department of Nephrology and Medical Intensive Care, Charite\u0301 \u2013 Universita\u0308tsmedizin Berlin, corporate member of Freie Universita\u0308t Berlin and Humboldt-Universita\u0308t zu Berlin , Berlin 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Berlin, Institute of Pharmacy , Berlin ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-9967-0108","authenticated-orcid":false,"given":"Sarah V","family":"Li\u00e9vano Contreras","sequence":"additional","affiliation":[{"name":"Max-Delbru\u0308ck-Center for Molecular Medicine in the Helmholtz Association , Berlin ,","place":["Germany"]},{"name":"DZHK (German Centre for Cardiovascular Research), partner site Berlin , Berlin ,","place":["Germany"]},{"name":"Max Rubner Center for Cardiovascular Metabolic Renal Research, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin , Berlin ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8719-938X","authenticated-orcid":false,"given":"Rongling","family":"Wang","sequence":"additional","affiliation":[{"name":"Max-Delbru\u0308ck-Center for Molecular Medicine in the Helmholtz Association , Berlin ,","place":["Germany"]},{"name":"DZHK (German Centre for Cardiovascular Research), partner site Berlin , Berlin ,","place":["Germany"]},{"name":"Max Rubner Center for Cardiovascular Metabolic Renal Research, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin , Berlin ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6841-4192","authenticated-orcid":false,"given":"Felix","family":"Behrens","sequence":"additional","affiliation":[{"name":"Experimental and Clinical Research Center (ECRC), a cooperation of Charite\u0301 \u2013 Universita\u0308tsmedizin Berlin and Max Delbr\u00fcck Center for Molecular Medicine , Berlin ,","place":["Germany"]},{"name":"Max-Delbru\u0308ck-Center for Molecular Medicine in the Helmholtz Association , Berlin ,","place":["Germany"]},{"name":"DZHK (German Centre for Cardiovascular Research), partner site Berlin , Berlin ,","place":["Germany"]},{"name":"Department of Nephrology and Medical Intensive Care, Charite\u0301 \u2013 Universita\u0308tsmedizin Berlin, corporate member of Freie Universita\u0308t Berlin and Humboldt-Universita\u0308t zu Berlin , Berlin ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8120-3306","authenticated-orcid":false,"given":"Bernd","family":"Hoppe","sequence":"additional","affiliation":[{"name":"German Hyperoxaluria Center , Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6385-2866","authenticated-orcid":false,"given":"Olivia","family":"Nonn","sequence":"additional","affiliation":[{"name":"Experimental and Clinical Research Center (ECRC), a cooperation of Charite\u0301 \u2013 Universita\u0308tsmedizin Berlin and Max Delbr\u00fcck Center for Molecular Medicine , Berlin ,","place":["Germany"]},{"name":"Max-Delbru\u0308ck-Center for Molecular Medicine in the Helmholtz Association , Berlin 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Angiology, and Intensive Care Medicine, Deutsches Herzzentrum der Charit\u00e9, Max Rubner Center for Cardiovascular Metabolic Renal Research (MRC) , Berlin ,","place":["Germany"]},{"name":"Translational Approaches in Heart Failure and Cardiometabolic Disease, Max Delbr\u00fcck Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7564-9937","authenticated-orcid":false,"given":"Franz","family":"Schaefer","sequence":"additional","affiliation":[{"name":"Division of Pediatric Nephrology, Department of Pediatrics I, Faculty of Medicine, University of Heidelberg, Heidelberg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8032-4096","authenticated-orcid":false,"given":"Johannes","family":"Holle","sequence":"additional","affiliation":[{"name":"Experimental and Clinical Research Center (ECRC), a 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Helmholtz-Center for Infection Research (HZI) and the Hannover Medical School (MHH) , Hannover ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8551-4729","authenticated-orcid":false,"given":"Alma","family":"Zernecke","sequence":"additional","affiliation":[{"name":"Institute of Experimental Biomedicine, University Hospital W\u00fcrzburg , Josef-Schneider-Str. 2, 97080 W\u00fcrzburg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3823-0920","authenticated-orcid":false,"given":"Kai-Uwe","family":"Eckardt","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Medical Intensive Care, Charite\u0301 \u2013 Universita\u0308tsmedizin Berlin, corporate member of Freie Universita\u0308t Berlin and Humboldt-Universita\u0308t zu Berlin , Berlin 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