Revolutionizing nephrocalcinosis treatment: IL-10 engineered macrophages as a novel therapeutic approach.

Nephrocalcinosis provides a nidus for stone formation and is strongly linked to renal injury and chronic kidney disease. Although the crucial role of macrophages in the formation and progression of calcium oxalate (CaOx) crystals has long been widely recognized, finding effective immunotherapies for nephrocalcinosis remains a challenge. In this study, we described an innovative macrophage-based method that delivers interleukin-10 (IL-10) into the kidney, reduces the deposition of CaOx crystals, and alleviates renal injury in a mouse model of glyoxylate-induced CaOx. Compared with recombinant IL-10 direct injection, the macrophage-based method has the advantages of biocompatibility and sustaining action. We found that the transplantation of engineered macrophages via the tail vein significantly reduced the volume of crystals in the kidney, thereby alleviating the kidney injury caused by crystal. In mechanistic studies, IL-10-secreting macrophages inhibited crystal formation and promoted crystal clearance by promoting macrophage M2 polarization, exerting a protective effect on renal tissue. Our data suggest that macrophage-based delivery of IL-10 to the kidney can be a potential treatment method for nephrocalcinosis.