Table 4.
Metabolic pathways required for T lymphocyte proliferation, differentiation, function, and activity.
| Immune cell | Metabolic pathway | Metabolic reprogramming | Relevance of metabolic pathway to cellular function | Model | References |
|---|---|---|---|---|---|
| αβ T cells | Glycolysis | ⇑ | Required for cell growth and clonal proliferation | (249) | |
| Glut1 transgenic mice Murine model of asthma |
(250) | ||||
| Oxidative phosphorylation | ⇑ | Required for the survival, proliferation, generation and function | (249) | ||
| Pentose phosphate pathway | ⇑ | Nucleotide and ribosome biosynthesis | (249) | ||
| TCA Cycle | ⇑ | (249) | |||
| Lipogenesis | ⇑ | Required for Th17 development, production of membrane phospholipids and inflammatory function | Pharmacological and genetic inhibition of ACC1 in mice Human T cell cultures Murine model of experimental autoimmune encephalomyelitis |
(251) | |
| Required for growth and proliferation | (249) | ||||
| Glutamine Metabolism | ⇑ | Regulates T cell activation | (249) | ||
| Fatty Acid Oxidation | ⇑ | Ex vivo human CD4+CD25−Foxp3− | (252) | ||
| ⇓ | Glut1 transgenic mice Murine model of asthma |
(250) | |||
| Regulatory T Cells | Glycolysis | ⇑ | Required for cellular migration | Treg-specific HIF-1α−/− mice | (253) |
| Required for cellular migration but not immunosuppressive function | Foxp3-GFP and Cd28Y170F genetically targeted mice on C57BL/6 background Ctla4−/− mice Murine lung microvascular endothelial cells, bone marrow-derived dendritic cells H2-d allospecific Treg cells Loss-of-function GCK mutation human blood samples |
(254) | |||
| Required for proliferation | Ex vivo CD4+CD25hiFoxp3+CD127− Treg cells | (252) | |||
| Lipogenesis | ⇓ | Pharmacological and genetic inhibition of ACC1 in mice Human T cell cultures Murine model of experimental autoimmune encephalomyelitis |
(251) | ||
| Fatty Acid Oxidation | ⇑ | Required for proliferation | Ex vivo CD4+CD25hiFoxp3+CD127− Treg cells | (252) | |
| Required for immunosuppressive activity | Treg-specific HIF-1α−/− mice | (253) | |||
| Glut1 transgenic mice Murine model of asthma |
(250) | ||||
| γδ T cells | Glycolysis | ⇑ | In γδ T1 cells and is required for differentiation and cytokine production | CD2-cre;Raptor-f/f mice | (255) |
| Oxidative phosphorylation | ⇑ | In γδ T17 cells and is required for the production of IL-17 | MyD88−/−, Il1r1−/− and IL-23R KO and conditional (CD2-cre; Raptorfl/fl, CD-2-cre;Rictorfl/fl and CD-2-cre;Stat3fl/fl) KO miceHuman subjects with psoriasis vulgarisPsoriasis-like mouse model | (256) | |
| TCA cycle | ⇑ | Required for the production of IL-17 | MyD88−/−, Il1r1−/−, and IL-23R KO and conditional (CD2-cre; Raptorfl/fl, CD-2-cre;Rictorfl/fl and CD-2-cre;Stat3fl/fl) KO mice Human subjects with psoriasis vulgaris Psoriasis-like mouse model |
(256) | |
| iNKT cells | Glycolysis | ⇑ | Required for the production of IFN-γ and TCR recycling and accumulation in the immune synapse | Murine spleen and liver Vα14 Tg.cxcr6gfp/+ iNKT cells | (257) |
| Oxidative PHOSPHORYLATION | ⇓ | Murine spleen and liver Vα14 Tg.cxcr6gfp/+ iNKT cells | (257) | ||
| ⇑ | Essential for survival, proliferation and selective cytokine production | PLZF+/− and PLFZTg mice spleen NKT cells | (258) | ||
| Pentose phosphate pathway | ⇑ | Required for effector functions | PLZF+/− and PLFZTg mice spleen NKT cells | (258) | |
| Lipogenesis | ⇑ | Required for the production of IFN-γ | Murine spleen Vα14 Tg.cxcr6gfp/+ iNKT cells Clinical tumor biospecimens from HCC patients |
(259) |
⇑, high metabolic rate; ⇓, low metabolic rate.