A kidney resident macrophage subset is a candidate biomarker for renal cystic disease in preclinical models

• Published in: Disease models & mechanisms Vol. 16; no. 1
• Main Authors: Li, Zhang, Zimmerman, Kurt A, Cherakara, Sreelakshmi, Chumley, Phillip H, Collawn, James F, Wang, Jun, Haycraft, Courtney J, Song, Cheng J, Chacana, Teresa, Andersen, Reagan S, Croyle, Mandy J, Aloria, Ernald J, Hombal, Raksha P, Thomas, Isis N, Chweih, Hanan, Simanyi, Kristin L, George, James F, Parant, John M, Mrug, Michal, Yoder, Bradley K
• Format: Journal Article
• Language: English
• Published: England The Company of Biologists Ltd 01-01-2023; The Company of Biologists
• Subjects: adpkd; Animal models; Animals; biomarker; Biomarkers; Bone marrow; cd206; CX3CR1 protein; Cysts; Disease; Disease Models, Animal; Flow cytometry; Kidney; Kidney diseases; Kidneys; Macrophages; Mice; Mice, Knockout; Mutants; Mutation; Polycystic kidney; Polycystic Kidney, Autosomal Dominant; renal disease and progression; renal macrophages; CD206; Renal disease and progression; ADPKD; Biomarker; Renal macrophages
• ISSN: 1754-8403; 1754-8411
• DOI: 10.1242/dmm.049810

Although renal macrophages have been shown to contribute to cyst development in polycystic kidney disease (PKD) animal models, it remains unclear whether there is a specific macrophage subpopulation involved. Here, we analyzed changes in macrophage populations during renal maturation in association with cystogenesis rates in conditional Pkd2 mutant mice. We observed that CD206+ resident macrophages were minimal in a normal adult kidney but accumulated in cystic areas in adult-induced Pkd2 mutants. Using Cx3cr1 null mice, we reduced macrophage number, including CD206+ macrophages, and showed that this significantly reduced cyst severity in adult-induced Pkd2 mutant kidneys. We also found that the number of CD206+ resident macrophage-like cells increased in kidneys and in the urine from autosomal-dominant PKD (ADPKD) patients relative to the rate of renal functional decline. These data indicate a direct correlation between CD206+ resident macrophages and cyst formation, and reveal that the CD206+ resident macrophages in urine could serve as a biomarker for renal cystic disease activity in preclinical models and ADPKD patients. This article has an associated First Person interview with the first author of the paper.