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.
Key points: Kidney tubular epithelial cells (TECs) have a high energy demand, relying primarily on fatty acid oxidation as an energy source.The metabolic and immune profile of TECs is affected by injury; further alterations occur with disease progression or repair processes.Following exposure to cellular stress, TECs rewire their metabolism, resulting in an accumulation of lipids and lipotoxicity.Activation of immunometabolic processes influence the response of TECs to stress; innate immune sensors act to sense immunological changes in the intracellular and extracellular environment but also regulate the metabolic needs, responses and phenotype of TECs.Targeting (immuno)metabolism through, for example, the targeting of innate immune sensors and their metabolic responses may represent a novel strategy for treating or preventing kidney disease.