Immunometabolic rewiring of tubular epithelial cells in kidney disease

Kidney tubular epithelial cells (TECs) have a crucial role in the damage and repair response to acute and chronic injury. To adequately respond to constant changes in the environment, TECs have considerable bioenergetic needs, which are supported by metabolic pathways. Although little is known about TEC metabolism, a number of ground-breaking studies have shown that defective glucose metabolism or fatty acid oxidation in the kidney has a key role in the response to kidney injury. Imbalanced use of these metabolic pathways can predispose TECs to apoptosis and dedifferentiation, and contribute to lipotoxicity and kidney injury. The accumulation of lipids and aberrant metabolic adaptations of TECs during kidney disease can also be driven by receptors of the innate immune system. Similar to their actions in innate immune cells, pattern recognition receptors regulate the metabolic rewiring of TECs, causing cellular dysfunction and lipid accumulation. TECs should therefore be considered a specialized cell type - like cells of the innate immune system - that is subject to regulation by immunometabolism. Targeting energy metabolism in TECs could represent a strategy for metabolically reprogramming the kidney and promoting kidney repair. The interplay between immunological and metabolic processes is important in a variety of processes. This Review describes how changes in lipid and energy metabolism, driven by receptors of the innate immune system, contribute to the response of tubule epithelial cells to injury and the functional consequences of these intersecting pathways in kidney health and disease.

Automated summary

Kidney tubular epithelial cells play a crucial role in the response to kidney injury and repair, and their metabolic abnormalities may contribute to kidney disease. Receptors of the innate immune system regulate the metabolic processes of these cells, and the interplay between immunometabolism and kidney health should be taken into consideration.