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Updated: Aug 15, 2026
Rapid Depletion of Renal Macrophages Using Human CD59/Intermedilysin Cell Ablation Tool
Published on: May 9, 2025
Conditional ablation of macrophages halts progression of crescentic glomerulonephritis
Jeremy S Duffield1, Peter G Tipping, Tiina Kipari
1Medical Research Council Centre for Inflammation Research Medical School, University of Edinburgh, UK, and the Renal Division, Brigham & Women's Hospital, Boston, MA 02115, USA. jduffield@rics.bwh.harvard.edu
Abstract:
The presence of macrophages in inflamed glomeruli of rat kidney correlates with proliferation and apoptosis of resident glomerular mesangial cells. We assessed the contribution of inflammatory macrophages to progressive renal injury in murine crescentic glomerulonephritis (GN). Using a novel transgenic mouse (CD11b-DTR) in which tissue macrophages can be specifically and selectively ablated by minute injections of diphtheria toxin, we depleted renal inflammatory macrophages through days 15 and 20 of progressive crescentic GN. Macrophage depletion reduced the number of glomerular crescents, improved renal function, and reduced proteinuria. Morphometric analysis of renal tubules and interstitium revealed a marked attenuation of tubular injury that was associated with reduced proliferation and apoptosis of tubular cells. The population of interstitial myofibroblasts decreased after macrophage depletion and interstitial fibrosis also decreased. In the presence of macrophages, interstitial myofibroblasts exhibited increased levels of both proliferation and apoptosis, suggesting that macrophages act to support a population of renal myofibroblasts in a high turnover state and in matrix deposition. Finally, deletion of macrophages reduced CD4 T cells in the diseased kidney. This study demonstrates that macrophages are key effectors of disease progression in crescentic GN, acting to regulate parenchymal cell populations by modulating both cell proliferation and apoptosis.
Insights
Inflammatory macrophages drive kidney damage in crescentic glomerulonephritis by promoting cell proliferation and apoptosis. Depleting these macrophages significantly improved kidney function and reduced injury, highlighting their central role in disease progression.
Area of Science:
- Nephrology
- Immunology
- Pathology
Background:
- Macrophages are present in inflamed glomeruli and correlate with mesangial cell proliferation and apoptosis.
- Inflammatory macrophages are implicated in progressive renal injury, particularly in crescentic glomerulonephritis (GN).
Purpose of the Study:
- To assess the contribution of inflammatory macrophages to progressive renal injury in murine crescentic GN.
- To investigate the role of macrophages in regulating parenchymal cell populations, proliferation, and apoptosis during GN.
Main Methods:
- Utilized a novel transgenic mouse model (CD11b-DTR) for specific and selective ablation of tissue macrophages.
- Administered diphtheria toxin to deplete renal inflammatory macrophages during progressive crescentic GN.
- Conducted morphometric analysis of renal tubules and interstitium, and assessed CD4 T cell populations.
Main Results:
- Macrophage depletion significantly reduced glomerular crescents, improved renal function, and decreased proteinuria.
- Attenuated tubular injury, reduced tubular cell proliferation and apoptosis, and decreased interstitial fibrosis were observed.
- Depletion of macrophages led to a decrease in interstitial myofibroblasts and CD4 T cells in the diseased kidney.
Conclusions:
- Macrophages are key effectors in the progression of crescentic GN.
- Macrophages regulate parenchymal cell populations by modulating both proliferation and apoptosis.
- Targeting macrophages may represent a therapeutic strategy for crescentic GN.
