Mechanisms of disrupted homeostasis and kidney injury

PROJECT SUMMARY Diabetic Kidney Disease (DKD) is the leading cause of kidney dysfunction and failure for more than 400 million patients worldwide. While the high prevalence of obesity is closely linked to the increased incidence of Type 2 diabetes, hypertension, and kidney failure, the complex interplay between these conditions is incompletely understood. Our recent work revealed an important role for a specialized group of cells in the kidney called TREM2 resident macrophages. These cells appear to increase in numbers in both mouse and human kidneys in the setting of obesity and diabetes. Therefore, the molecule TREM2 that is found on the surface of these immune cells may be a therapeutic target for kidney disease. The goal of this proposal is to build on our recent discoveries and perform detailed studies in mouse models and human kidney tissue to gain further insight into whether TREM2 macrophages can protect the kidney from the harmful effects of obesity-driven type 2 diabetes. This work will pave the way for new therapies for diabetic kidney disease patients, which are greatly needed.