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A chronic high phosphate diet (HPD) in mice increases serum levels of phosphate and fibroblast growth factor 23 (FGF23) which is associated with progressive tubule damage and fibrosis. We hypothesized that chronic HPD induces TLS in the kidneys and thereby promotes progressive kidney injury. After only 2\u2009months, mice on HPD showed increased tubule damage accompanied by the formation of perivascular immune cell clusters of B and T cells in the corticomedullary zone and in the cortex. In addition, lymphatic vessels were observed, accompanied by increased expression of venous markers and cell adhesion molecules. Further analyses showed a time\u2010dependent induction of the immunofibroblast\u2010derived chemokines and lymphotoxins, which are important for the differentiation of immunofibroblasts into follicular dendritic cells (FDC) and fibroblastic reticular cells (FRC). Already after 4\u2009months of HPD, proliferating B\u2010cell clusters with FDCs, T\u2010cell clusters with FRCs, podoplanin\n                    <jats:sup>+<\/jats:sup>\n                    cellular networks, high endothelial venules, plasma cells and increased IgD synthesis indicated fully mature TLSs, while tubular damage and fibrosis continued to increase up to 6\u2009months of feeding HPD. Genetically modified mice overexpressing FGF23 developed tubular damage, fibrosis, and fully mature TLS only in the presence of HPD\u2010induced hyperphosphatemia. Likewise, hypophosphatemic\n                    <jats:italic>Hyp<\/jats:italic>\n                    mice showed no signs of tubular damage or TLS despite increased FGF23 levels. Our data suggest that high phosphate directly causes chronic inflammation in the kidney leading to the development of fully mature TLS associated with progressive tubular injury.\n                  <\/jats:p>","DOI":"10.1096\/fj.202500968r","type":"journal-article","created":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T15:00:06Z","timestamp":1765551606000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["High Phosphate Load Induces De Novo Formation of Tertiary Lymphoid Structures in the Kidney"],"prefix":"10.1096","volume":"39","author":[{"given":"Nina","family":"Weing\u00e4rtner","sequence":"first","affiliation":[{"name":"Department of Pediatric Kidney, Liver, Metabolic and Neurological Diseases, Pediatric Research Center Hannover Medical School  Hannover 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