TAX1BP1 limits macrophage-myofibroblastlast transition in lupus kidney fibrosis

Lupus nephritis causes kidney failure in systemic lupus erythematosus. We asked whether raising levels of the TAX1BP1 could slow this damage. Using mice with lupus-like disease, we delivered a gene therapy that increased TAX1BP1 in kidney tubule cells. After four weeks, treated animals showed smaller lymph nodes and spleens, lower anti-DNA antibodies and serum creatinine, and less protein in the urine. Kidney fibrosis, judged by collagen staining, was markedly reduced. Single-cell sequencing revealed that TAX1BP1 was highest in proximal tubule cells and linked to decreased Galectin-3, a known driver of fibrosis. Immunofluorescence confirmed lower Galectin-3 and fewer α-SMA + macrophages, indicating fewer cells transitioning into myofibroblasts. We conclude that boosting TAX1BP1 in proximal tubule cells limits kidney fibrosis by reducing Galectin-3 and blocking macrophage-to-myofibroblast transition, offering a potential new strategy against lupus nephritis.