Grants and Contributions:

Grant or Award spanning more than one fiscal year. (2017-2018 to 2022-2023)

The kidney is a complex organ due to the “in series” organization of its various tubular segments. The collecting duct runs through the renal cortex (cortical collecting duct) and then the medulla (outer and inner medulla) prior to releasing final urine in the renal pelvis. It is composed of at least three different cell types: principal cells (PC), type-A and type-B intercalated cells (IC). While textbooks currently describe principal cells as mediating sodium and water reabsorption, and IC as responsible for acid-base homeostasis, recent in vivo findings support more versatile functions for these various cell types. We thus have to re-evaluate the function(s) of each cell type to normal renal physiology.

Recent studies support that in addition to their acid-secreting function, type-A IC also play an essential role in innate immunity against uropathogenic E. coli (UPEC). Further, type-A IC in the outer medullary collecting duct can remodel into dendritic-like cells with lateral cytoplasmic projections, supporting that type-A IC may play more than just one role in acid-base homeostasis in renal physiology. However, at this time the intracellular and extracellular machinery that results in the cellular remodeling of IC’s function to innate immunity is unknown.

The long-term objective of this program is to decipher the multiple and complementary roles of intercalated and principal cell types in renal physiology. Our short-term objective is to dissect the cellular mechanisms that regulate the role IC play in normal renal physiology, in particular in innate immunity. This program has no conceptual or budgetary overlap with our currently funded research and is an independent research arm that we aim to develop in the next decade. Using cell biology and biochemical approaches on immortalized cell models of medullary IC, we will identify the UPEC attachment site to IC, and dissect the resulting intracellular signalling pathway(s), the hormonal regulation and cellular remodelling that lead to IC-mediated renal protection. Results from this program will contribute to a better understanding of the role(s) of IC in renal physiology and immunity.