1. Figure 4 Immune regulatory roles of glycolytic intermediates
Figure 4 | Immune regulatory roles of glycolytic intermediates. Glycolytic intermediates not only influence immune function and inflammation by their role in metabolism, but also by specifically regulating various processes. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) also functions as an RNA-binding molecule that can inhibit the translation of IFNG and IL2 mRNA. High glycolytic flux forces excess GAPDH into the glycolytic process, thereby relieving RNA from inhibition. Reduction of glycolytic flux releases enolase from the glycolytic pathway, upon which it enters the nucleus to aid the formation of the alternative splice variant of the transcription factor FOXP3, FOXP3-E2, generating potently immunosuppressive induced regulatory T (iTreg) cells. The glycolytic intermediate 2-phosphoenolpyruvate promotes Ca2+ signalling, which supports T cell activation during high rates of glycolysis. When the M2 isoenzyme of pyruvate kinase (PKM2) is activated as a tetramer, it supports flux through glycolysis into the tricarboxylic acid cycle. As a dimer, PKM2 either acts as co-activator of hypoxia-inducible factor 1α, or it supports signal transduction by phosphorylating signal transducer and activator of transcription 3, which both support proinflammatory immune responses.
Gaber, T. et al. (2017) Metabolic regulation of inflammation
Nat. Rev. Rheumatol. doi: /nrrheum