Study reveals how kidneys rebuild immune defenses after injury

The kidneys filter about 50 gallons of blood every day, removing waste while helping regulate blood pressure, balance fluid levels and serve other vital functions. But when those organs are damaged by illness or injury, a specialized group of immune cells helps determine whether the kidneys recover or sustain lasting damage.

Acute kidney injury is a common complication of severe infections, surgery, trauma, dehydration or reduced blood flow to the kidneys, accounting for roughly 1 in 5 hospitalized adults. Even when patients survive the initial injury, incomplete healing can increase the risk of chronic kidney disease.

Now, researchers at Tulane University have uncovered new details about how those immune cells rebuild themselves after being depleted, offering new insight into the body's natural repair process and laying the foundation for future therapies for kidney disease.

The study, led by Xuebin Qin, professor of microbiology and immunology at the Tulane National Biomedical Research Center, appears in the journal Cells.

The research focused on kidney-resident macrophages, immune cells that serve as the kidney's first responders. In healthy kidneys, these cells remove dead tissue, monitor for infection and help coordinate healing following injury.

Until now, scientists understood relatively little about how this network is restored after those macrophages are lost.

Using a unique and specialized mouse model and single-cell RNA sequencing, Qin and colleagues tracked individual immune cells as they repopulated the kidney over time. Rather than simply replacing missing cells, the team found that kidney cells and macrophages engage in an intricate molecular conversation that guides the rebuilding process.

The researchers discovered that kidney epithelial cells - protective cells that line the kidney and other organs - quickly begin producing chemical signals that recruit new macrophages. As those cells return, they gradually shift from an early inflammatory state into cells that support tissue repair. Throughout the process, macrophages and neighboring kidney cells continuously exchange signals that help restore a healthy immune environment.

"Understanding how the kidney naturally rebuilds its immune system after injury is essential if we hope to develop therapies that improve recovery," Qin said.

By identifying the molecular signals that coordinate kidney repair, the findings could help researchers develop new approaches to promote healing and reduce long-term kidney damage.

The study also builds on earlier work from Qin's laboratory helped define the origins and a variety of kidney-resident macrophages. Together, the research provides an increasingly detailed picture of how these specialized immune cells maintain kidney health before, during and after injury.

The research was conducted by investigators from the Tulane National Biomedical Research Center and the Tulane University School of Medicine. The study was supported by the National Institutes of Health under awards P51OD011104 and R01DK129881.