Metabolic mysteries of the inflammatory response: T cell polarization and plasticity.
While simultaneously maintaining homeostasis and reducing further harm to the host, the immune system is equipped to eliminate both tumors and pathogenic microorganisms. Bifurcated into cell-mediated and humoral immunity, the adaptive immune system requires a series of complex and coordinated signals to drive the proliferation and differentiation of appropriate subsets. These include signals that modulate cellular metabolism. When first published in the 1920s, "the Warburg effect" was used to describe a phenomenon in which most cancer cells relied on aerobic glycolysis to meet their biosynthetic demands. Despite the early observations of Warburg and his colleagues, targeting cancer cell metabolism for therapeutic purposes still remains theoretical. Notably, many T cells exhibit the same Warburg metabolism as cancer cells and the therapeutic benefit of targeting their metabolic pathways has since been reexamined. Emerging evidence suggests that specific metabolic alterations associated with T cells may be ancillary to their subset differentiation and influential in their inflammatory response. Thus, T cell lymphocyte activation leads to skewing in metabolic plasticity, and issue that will be the subject of this review.
UC Irvine, MB&B, 3140 McGaugh Hall, Irvine, CA, USA.
Kelley M
KM
Fracchia
Craig M
CM
Walsh
D002454:Cell Differentiation; D049109:Cell Proliferation; D005786:Gene Expression Regulation; D005947:Glucose / Q000276:immunology / Q000378:metabolism*; D051272:Glucose Transporter Type 1 / Q000235:genetics / Q000276:immunology; D006019:Glycolysis / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D020738:Leptin / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation; D010085:Oxidative Phosphorylation; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*
D051272:Glucose Transporter Type 1; D020738:Leptin; C495677:SLC2A1 protein, human; D005947:Glucose
T cells; aerobic glycolysis; glucose; glycolysis; immunity; metabolism; oxidative phosphorylation