Table 1.

Metabolic pathways used by the innate and adaptive immune cells

Immune cell subsetMetabolic pathway(s)Factor(s) regulatedRole in immune cell development and functionReferences
Cytotoxic CD8+ T cell Glycolysis mTORC1; Myc Activation and polarization to gain killing ability Araki et al., 2009; Wang et al., 2011  
SREBP Heightened glycolytic metabolism and respiratory capacity during blastogenesis Kidani et al., 2013  
FAO PPAR Increased FAO leading to enhanced anti-tumor immunity Chowdhury et al., 2018  
FAS ACAT1 Effector molecule production and TCR engagement Yang et al., 2016  
SREBP; mTOR Membrane synthesis, activation, and expansion Kidani et al., 2013  
Glutaminolysis Myc Link with multiple biosynthetic pathways Wang et al., 2011  
NK cell Glycolysis mTOR; c-Myc Effector molecule (especially IFN-γ) production; maintain killing ability and mitochondrial mass Donnelly et al., 2014; Marçais et al., 2014; Düvel et al., 2010  
TGF-β; FBP1 Slattery and Gardiner, 2019; Zaiatz-Bittencourt et al., 2018  
SREBP Effector molecule production and cytotoxicity (controlled through the CMS) Assmann et al., 2017  
FAO PPAR-α/δ Effector molecule production; immunosurveillance against tumor growth; maintain mitochondrial mass and membrane potential Michelet et al., 2018  
PPAR-γ Kobayashi et al., 2020  
Th1 Glycolysis GLUT1; mTOR/Akt Polarization and maintenance Delgoffe et al., 2009; Macintyre et al., 2014  
FAS ACC1 Expansion and infiltration Mamareli et al., 2021  
Th2 Glycolysis mTOR/Akt Polarization and maintenance Delgoffe et al., 2009  
FAO PPAR-γ IL-9 expression Micossé et al., 2019; von Meyenn et al., 2019  
FAS ACC1 Development of IL-5–producing Th2 cells in lung and skin Nakajima et al., 2021  
Th17 Glycolysis GLUT1; mTOR/Akt; HIF-1α Polarization and proliferation Delgoffe et al., 2009; Macintyre et al., 2014; Shi et al., 2011  
FAS ACC1 Expansion and infiltration Mamareli et al., 2021  
ILC1 Unknown TGF-β ILC1-related plasticity Fuchs et al., 2013  
ILC2 FAO PPAR-α; FATP6 Maintain IL-13 production in the context of helminth infection or malnutrition Wilhelm et al., 2016  
Lipid synthesis PPAR-γ; DGAT1 Lipid droplet formation, mitochondrial function, and proliferation Karagiannis et al., 2020  
Glycolysis mTOR Control PPAR-γ and DGAT1 expression; proliferation and cytokine production Karagiannis et al., 2020  
PKM2; HIF-1α Induction of IL-33 receptor; maturation and function Li et al., 2018; Surace et al., 2021a  
Arg-1 Glycolytic capacity, proliferation, and pro-inflammatory functions Monticelli et al., 2016  
OXPHOS Branched amino acid; arginine Maintain cellular fitness and proliferation Surace et al., 2021a  
ILC3 Glycolysis mTOR and ROS Development, proliferation, and activation Di Luccia et al., 2019  
HIF-1α Cytokine production and switch to glycolysis Fachi et al., 2021  
FAS ACC1 RORγt expression; cytokine production and lipogenesis Mamareli et al., 2021  
Immune cell subsetMetabolic pathway(s)Factor(s) regulatedRole in immune cell development and functionReferences
Cytotoxic CD8+ T cell Glycolysis mTORC1; Myc Activation and polarization to gain killing ability Araki et al., 2009; Wang et al., 2011  
SREBP Heightened glycolytic metabolism and respiratory capacity during blastogenesis Kidani et al., 2013  
FAO PPAR Increased FAO leading to enhanced anti-tumor immunity Chowdhury et al., 2018  
FAS ACAT1 Effector molecule production and TCR engagement Yang et al., 2016  
SREBP; mTOR Membrane synthesis, activation, and expansion Kidani et al., 2013  
Glutaminolysis Myc Link with multiple biosynthetic pathways Wang et al., 2011  
NK cell Glycolysis mTOR; c-Myc Effector molecule (especially IFN-γ) production; maintain killing ability and mitochondrial mass Donnelly et al., 2014; Marçais et al., 2014; Düvel et al., 2010  
TGF-β; FBP1 Slattery and Gardiner, 2019; Zaiatz-Bittencourt et al., 2018  
SREBP Effector molecule production and cytotoxicity (controlled through the CMS) Assmann et al., 2017  
FAO PPAR-α/δ Effector molecule production; immunosurveillance against tumor growth; maintain mitochondrial mass and membrane potential Michelet et al., 2018  
PPAR-γ Kobayashi et al., 2020  
Th1 Glycolysis GLUT1; mTOR/Akt Polarization and maintenance Delgoffe et al., 2009; Macintyre et al., 2014  
FAS ACC1 Expansion and infiltration Mamareli et al., 2021  
Th2 Glycolysis mTOR/Akt Polarization and maintenance Delgoffe et al., 2009  
FAO PPAR-γ IL-9 expression Micossé et al., 2019; von Meyenn et al., 2019  
FAS ACC1 Development of IL-5–producing Th2 cells in lung and skin Nakajima et al., 2021  
Th17 Glycolysis GLUT1; mTOR/Akt; HIF-1α Polarization and proliferation Delgoffe et al., 2009; Macintyre et al., 2014; Shi et al., 2011  
FAS ACC1 Expansion and infiltration Mamareli et al., 2021  
ILC1 Unknown TGF-β ILC1-related plasticity Fuchs et al., 2013  
ILC2 FAO PPAR-α; FATP6 Maintain IL-13 production in the context of helminth infection or malnutrition Wilhelm et al., 2016  
Lipid synthesis PPAR-γ; DGAT1 Lipid droplet formation, mitochondrial function, and proliferation Karagiannis et al., 2020  
Glycolysis mTOR Control PPAR-γ and DGAT1 expression; proliferation and cytokine production Karagiannis et al., 2020  
PKM2; HIF-1α Induction of IL-33 receptor; maturation and function Li et al., 2018; Surace et al., 2021a  
Arg-1 Glycolytic capacity, proliferation, and pro-inflammatory functions Monticelli et al., 2016  
OXPHOS Branched amino acid; arginine Maintain cellular fitness and proliferation Surace et al., 2021a  
ILC3 Glycolysis mTOR and ROS Development, proliferation, and activation Di Luccia et al., 2019  
HIF-1α Cytokine production and switch to glycolysis Fachi et al., 2021  
FAS ACC1 RORγt expression; cytokine production and lipogenesis Mamareli et al., 2021  

PI3K, phosphoinositide 3-kinase; STAT6, signal transducer and activator of transcription 6; FBP1, gluconeogenic enzyme FBP1.

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