Role of mast cells in experimental anti‐glomerular basement membrane glomerulonephritis

Recently, divergent reports on the role of mast cells (MC) in different glomerular diseases have brought our attention to their role in an accelerated model of anti‐glomerular basement membrane (GBM) glomerulonephritis (GN). Genetically MC‐deficient KitW/KitW‐v mice, MC‐reconstituted KitW/KitW‐v mice and Kit+/+ control mice were subjected to anti‐GBM GN. Kit+/+ mice developed moderate proteinuria and glomerular damage following the induction of anti‐GBM nephritis. In contrast, proteinuria and glomerular damage were dramatically increased in MC‐deficient KitW/KitW‐v mice. MC‐reconstituted KitW/KitW‐v mice showed proteinuria and glomerular damage comparable to Kit+/+ mice. A significant increase in infiltrating T cells and macrophages was detected in MC‐deficient KitW/KitW‐v mice as compared to Kit+/+ control mice and MC‐reconstituted KitW/KitW‐v mice. Accordingly, we observed an increase of TGF‐β1 mRNA in kidneys from KitW/KitW‐v mice. Interestingly, we did not detect MC in the kidney using either Giemsa staining or RT‐real‐time PCR, but MC were found in the regional lymph nodes. Finally, mortality of KitW/KitW‐v mice was significantly increased after the induction of anti‐GBM GN due to uremia. Our report provides the first direct evidence that MC are protective in anti‐GBM GN, possibly by modulating the influx of effector T cells and macrophages to inflammatory sites in the kidney.