LAUSR

Environmental cues are a major component of directing immune function in health and disease. Cells sense their environment in part through recognition of small molecules such as cytokines, chemokines, and pathogen-associated molecular pattern (PAMP) molecules. This provides immune cells instruction on how to respond to different inflammatory situations. Recent studies in immunometabolism have identified nutrient availability (i.e., glucose or other carbon sources, amino acids, lipids) as an important environmental cue, especially in activated, highly metabolic immune cells (1). Related to nutrients is oxygen, which is critical for most multicellular life as an essential element of several biochemical pathways for the generation of cellular energy. Cells are able to sense oxygen levels and modulate their biosynthetic and transcriptional pathways accordingly. Cells have two major pathways for generating energy from a carbon source: oxidative phosphorylation or glycolysis. Oxygen is essential for oxidative phosphorylation, the metabolic pathway in which energy is generated through the electron transport chain in mitochondria. In contrast, glycolysis is less fuel efficient but can proceed in the absence of oxygen. In most cells, glycolysis is reserved for when oxygen is limited. However, like tumor cells, activated T cells are able to undergo glycolysis even in the presence of oxygen, a process termed aerobic glycolysis (1). As such, T cells have a distinct relationship with oxygen and modulate their function in response to environmental oxygen levels.