Table 1. Metabolic pathways used by the... | Rockefeller University Press

Table 1.

Metabolic pathways used by the innate and adaptive immune cells

Immune cell subset	Metabolic pathway(s)	Factor(s) regulated	Role in immune cell development and function	References
Cytotoxic CD8⁺ T cell	Glycolysis	mTORC1; Myc	Activation and polarization to gain killing ability	Araki et al., 2009; Wang et al., 2011
	Glycolysis	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
	FAS	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
	FAO	PPAR-γ		Kobayashi et al., 2020
Th1	Glycolysis	GLUT1; mTOR/Akt	Polarization and maintenance	Delgoffe et al., 2009; Macintyre et al., 2014
Th1	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
Th17	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
	Glycolysis	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 subset	Metabolic pathway(s)	Factor(s) regulated	Role in immune cell development and function	References
Cytotoxic CD8⁺ T cell	Glycolysis	mTORC1; Myc	Activation and polarization to gain killing ability	Araki et al., 2009; Wang et al., 2011
	Glycolysis	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
	FAS	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
	FAO	PPAR-γ		Kobayashi et al., 2020
Th1	Glycolysis	GLUT1; mTOR/Akt	Polarization and maintenance	Delgoffe et al., 2009; Macintyre et al., 2014
Th1	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
Th17	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
	Glycolysis	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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