Table 1.

Pharmacological inhibitors of the energy‐generating metabolic pathways and their regulators in Tregs, effects and diseases applied

Metabolic Pathway	Target	Drug	Effect on Tregs	Associated Disease	Species	Reference
Glucose metabolism	Glut‐1	CG‐5	Induce Treg differentiation	SLE	Mouse	[99]
	Glycolysis	2‐DG	Induce Treg differentiation and suppression	Experimental autoimmune neuritis	Mouse	[102]
				Skin and heart transplantation	Mouse	[105]
	PDHK	DCA	Increase Treg expansion	EAE	Mouse	[55]
	One‐carbon metabolism	Methotrexate	Increase Treg expansion	Rheumatoid arthritis, psoriasis, Crohn's disease and multiple sclerosis	Human	[39]
Lipid Metabolism	Mevalonate pathway	Statins	Dampen Treg stability and function
	PPARγ (FA oxidation)	Pioglitazone	Induce VAT Tregs	Obesity	Mouse	[77]
	ACC (FA synthesis)	Soraphen A	Induce Treg differentiation	EAE	Mouse	[70]
	ACC (FA synthesis)	TOFA	Impair Treg proliferation	Glioblastoma	Mouse	[117]
	Lipid uptake	SSO	Impair Treg suppression
Glutamine Metabolism	Glutamine uptake	DON	In combination with metformin and 2‐DG, promote Treg generation	Skin and heart transplantation	Mouse	[105]
Metabolic Regulators	mTORC1	Rapamycin	Increase Treg stability, generation and function	Graft rejection	Human	[26, 27]
				Autoimmune phenotype	Mouse	[61]
	AMPK	Metformin	Induce Treg differentiation	Type II diabetes	Human	[103]
				Skin and heart transplantation	Mouse	[105]
				Inflammatory bowel disease	Mouse	[103]
				EAE	Mouse	[104]
	mtROS	MitoTEMPO	Inhibit Treg damage and apoptosis	EAE	Mouse	[107]

SLE, Systemic lupus erythematosus; 2‐DG, 2‐Deoxy‐D‐Glucose; PDHK, Pyruvate dehydrogenase kinase; DCA, Dichloroacetate; EAE, Experimental autoimmune encephalomyelitis; SSO, Sulfo‐N‐succinimidyl oleate; TOFA, 5‐tetradecyl‐oxy‐2‐furoic acid, ACC: Acetyl‐CoA carboxylase; DON, 6‐diazo‐5‐oxo‐L‐norleucine; mtROS, mitochondrial reactive oxygen species.