Grant: Master's Award: Canada Graduate Research Scholarships - Master's program

The immune system plays a key role in inflammation and repair during acute kidney injury (AKI), and exacerbated inflammation can lead to chronic kidney disease (CKD). Macrophages are a type of innate immune cell that reside within all tissues, including the kidneys, patrolling for foreign threats and participating in tissue development and homeostasis. We previously defined three conserved macrophage subsets within tissues, including a subset with embryonic origin and roles in tissue repair and regeneration. This subset was thought to be absent in the kidney, however, recent findings identified their presence in the renal capsule. The renal capsule is a fibrous tissue encapsulating the parenchyma with little known role. Although the capsule is vastly understudied, previous work suggests its removal leads to poor recovery from AKI and that cells are capable of re-localization from the capsule to the parenchyma. However, the mechanisms by which the capsule is protective to AKI, and the cell types involved, are unknown. We hypothesize the renal capsule represents a unique niche for tissue resident macrophages that have a critical role in repair following AKI. We will utilize mouse models of AKI and genetic fate mapping approaches to understand the developmental relationship and disparate functions capsule macrophages have in relation to inflammatory monocyte-derived macrophages. We will employ complementary microscopy and transcriptomic techniques to visualize capsule macrophage migration and gain insight into the mechanisms by which capsule macrophages respond to injury. Overall, this work will advance our understanding of a novel population of renal capsule macrophages and their role in AKI leading to innovative approaches for slowing CKD and improving patient outcomes.