Kidney macrophages keep the stones rolling

The kidney tubulointerstitium is densely populated by mononuclear phagocytes (MNP), including macrophages and dendritic cells. 1 Nelson P.J. Rees A.J. Griffin M.D. et al. The renal mononuclear phagocytic system. J Am Soc Nephrol. 2012; 23: 194-203 Crossref PubMed Scopus (214) Google Scholar These immune cells develop from yolk sac-derived precursors in early life and are later gradually replaced by bone marrow-derived cells. They enter the kidney by using the chemokine receptor CX3CR1 in mice and take residence in the tubulointerstitial space between tubular epithelial cells and capillaries. 2 Hochheiser K. Heuser C. Krause T.A. et al. Exclusive CX3CR1 dependence of kidney DCs impacts glomerulonephritis progression. J Clin Invest. 2013; 123: 4242-4254 Crossref PubMed Scopus (83) Google Scholar ,3 Lionakis M.S. Swamydas M. Fischer B.G. et al. CX3CR1-dependent renal macrophage survival promotes Candida control and host survival. J Clin Invest. 2013; 123: 5035-5051 Crossref PubMed Scopus (178) Google Scholar Generally, macrophages and dendritic cells are present in all organs and possess diverse homeostatic, defensive and reparative functions. MNP with dendritic cell functionality are predominantly present in the kidney cortex, and have been implicated in the progression of chronic glomerulonephritis by stimulating nephritogenic T lymphocytes 4 Kurts C. Ginhoux F. Panzer U. Kidney dendritic cells: fundamental biology and functional roles in health and disease. Nat Rev Nephrol. 2020; 16: 391-407 Crossref PubMed Scopus (60) Google Scholar . MNP in the medulla are more macrophage-like and survey their environment for signs of injury, sterile inflammation or pyelonephritis, to which they respond by recruiting immune cells with reparative or defensive functionality, like monocytes or neutrophils, respectively 2 Hochheiser K. Heuser C. Krause T.A. et al. Exclusive CX3CR1 dependence of kidney DCs impacts glomerulonephritis progression. J Clin Invest. 2013; 123: 4242-4254 Crossref PubMed Scopus (83) Google Scholar . Furthermore, they were shown to capture circulating immune complexes that precipitated on tubulointerstitial endothelial cells, which may impact immune-complex-induced nephritis 5 Stamatiades E.G. Tremblay M.E. Bohm M. et al. Immune Monitoring of Trans-endothelial Transport by Kidney-Resident Macrophages. Cell. 2016; 166: 991-1003 Abstract Full Text Full Text PDF PubMed Scopus (149) Google Scholar . Medullary macrophages were also shown to phagocytose intratubular crystals, which tend to precipitate in an acidic and hyperosmolar microenvironment, resulting in inflammasome activation, chronic sterile inflammation and in the long run, kidney fibrosis 6 Knauf F. Asplin J.R. Granja I. et al. NALP3-mediated inflammation is a principal cause of progressive renal failure in oxalate nephropathy. Kidney Int. 2013; 84: 895-901 Abstract Full Text Full Text PDF PubMed Scopus (168) Google Scholar . In a recently published study, He and colleagues report a novel and unexpected function of macrophages in the renal medulla, i.e. to capture particles from the tubular lumen and to prevent the formation of kidney stones 7 He J. Cao Y. Zhu Q. et al. Renal macrophages monitor and remove particles from urine to prevent tubule obstruction. Immunity. 2024; 57: 106-123.e107 Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar .