Studies identify immune cell types associated with progression of different forms of kidney disease
A recent study of chronic kidney disease (CKD) in mice shows that one type of immune cell may have an important role in accelerating kidney fibrosis, or scarring, which can lead to kidney failure, while another study linked a group of immune cell types to accelerated cyst growth after kidney injury in a mouse model of cystic kidney disease.
The immune system is thought to drive inflammation leading to kidney fibrosis and loss of function in common forms of CKD, but the mechanisms by which it does so have not been well understood. A group of researchers therefore examined kidney cells of male mice with CKD that were showing signs of inflammation and fibrosis and discovered the cells were secreting a factor that attracts a type of immune cell known as a basophil.
In further experiments, they found that they could slow the process of fibrosis by reducing the number of basophils in the animals or interfering with the basophils’ ability to signal to other cells. Notably, an analysis of kidney cells from people with and without CKD showed that CKD was associated with substantially higher basophil levels and that higher basophil levels correlated with more fibrosis. These results suggest that basophils may play an important role in the progression of common forms of kidney disease, and that it may one day be possible to slow CKD progression by interfering with basophils.
Another group of researchers sought to investigate the role of various immune cells in the progression of cystic kidney diseases like autosomal dominant polycystic kidney disease (ADPKD). Previous research had suggested that kidney inflammation caused by injury or infection results in rapid acceleration of the disease by promoting both the formation and growth rate of cysts. The researchers therefore examined female mice with a model of cystic kidney disease and found several differences in the proportion of different types of immune cells between healthy kidneys, kidneys with slow-growing cysts, and kidneys where cysts grew rapidly due to injury. In particular, there were differences in a group of immune cells associated with adaptive immunity (i.e., cells that acquire the ability to fight an infection from previous exposure to the same pathogen). To explore the roles of these cells in kidney cyst growth, they used a technique to eliminate adaptive immune cells from the mice. Interestingly, kidney injury did not lead to the usual acceleration of cystic disease in mice without the adaptive immune cells, while the absence of these cells did not affect disease progression in uninjured kidneys. If these cells are found to have similar effects on human kidney cysts, it may one day be possible to protect people with ADPKD or other cystic kidney diseases from rapid disease progression after injury or infection by modulating the activities of specific groups of immune cells.
Doke T, Abedini A, Aldridge DL, …Susztak K. Single-cell analysis identifies the interaction of altered renal tubules with basophils orchestrating kidney fibrosis. Nat Immunol 23: 947-959, 2022.
Song CJ, Li Z, Ahmed UKB, …Zimmerman KA. A comprehensive immune cell atlas of cystic kidney disease reveals the involvement of adaptive immune cells in injury-mediated cyst progression in mice. J Am Soc Nephrol 33: 747-768, 2022.