Mini reviewMYC and HIF in shaping immune response and immune metabolism

- MYC and HIF1 are involved in regulating T cell development, activation and differentiation.
- Antigen and immune stimuli drive T cell metabolic rewiring to meet the demand on energy, macromolecule synthesis and redox.
- MYC and/or HIF1 act to coordinate T cell metabolic reprogramming, proliferation and differentiation, enabling an adaptive immune response.

Upon antigen stimulation, quiescent naive T cells undergo a phase of cell mass accumulation followed by cell cycle entry, clonal expansion, differentiation into functional subsets and back again to a quiescent state as they develop into memory cells. The transitions between these distinct cellular states place unique metabolic demands on energy, redox and biosynthesis. To fulfill these demands, T cells switch back and forth between their primary catabolic pathways. While quiescent naive and memory T cells largely rely on the oxidation of fatty acids and glucose, active T cells rely on glycolysis and glutaminolysis to sustain cell growth, proliferation and differentiation. Beyond several key signaling kinase cascades, the hypoxia inducible factor 1 (HIF-1) and the proto-oncogene MYC, act alone or in concert, to coordinate T cell metabolic reprogramming, cell proliferation, functional differentiation and apoptosis, enabling a robust T cell-mediated adaptive immune response.

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