Cutting edge: distinct glycolytic and lipid oxidative metabolic programs are essential for effector and regulatory CD4+ T cell subsets
What this study shows
Comparing CD4 T cells grown under effector and regulatory conditions, the authors showed that Th1, Th2 and Th17 cells carry high surface Glut1 and are strongly glycolytic, while inducible Treg carry little Glut1, oxidise lipid at a higher rate and have more phosphorylated AMPK. Blocking lipid oxidation with etomoxir selectively suppressed Treg generation and left effector differentiation intact, whereas removing glucose blocked Th17 but not Treg. Both rapamycin and metformin raised fatty acid oxidation in stimulated CD4 T cells, and etomoxir prevented the Treg increase produced by rapamycin or TGF-beta, which ties the pro-Treg effect of mTOR inhibition to lipid oxidation. In a mouse asthma model, metformin lowered Glut1 on activated CD4 T cells and increased the proportion and number of Treg in draining lymph nodes, although airway responsiveness itself did not change significantly. Boundary: mouse cells and one mouse allergic-airway model; mTOR inhibition is pharmacological (rapamycin) and mTOR activity was not measured directly, so the mTOR arm is inferred from drug effects.
At a glance
| Evidence type | M Molecular — cells, biochemistry, structure Marked M because it is molecular or in-vitro work (model: Primary mouse CD4 T cells polarised in vitro to Th1, Th2, Th17 and inducible Treg, with rapamycin, metformin or the CPT1 inhibitor etomoxir; Glut1-transgenic and Glut1-myc knock-in mice; OVA-driven allergic asthma model with metformin) rather than a whole-organism health-outcome study. That is often exactly where causal biology gets established -- the code says which system the finding was shown in, and nothing about how good the work is. |
| Study type | 5 - Mechanistic / In Vitro |
| Model system | Primary mouse CD4 T cells polarised in vitro to Th1, Th2, Th17 and inducible Treg, with rapamycin, metformin or the CPT1 inhibitor etomoxir; Glut1-transgenic and Glut1-myc knock-in mice; OVA-driven allergic asthma model with metformin |
| Journal | Journal of Immunology |
| Year | 2011 |
| Peer reviewed | Yes |
| Record last updated | 2026-10-01 |
| Source | DOI 10.4049/jimmunol.1003613 · PMID 21317389 · Free full text (PMC3198034) |
Extracted findings
These fields were extracted from the paper with AI assistance and have not been checked against the source. Read them as a pointer into the paper, not as curated claims; where they disagree with the curated summary above, the curated summary stands.
| Intervention | Rapamycin (25 nM), metformin (100 uM in vitro, 250 mg/kg daily in vivo), etomoxir (200 uM), glucose withdrawal, Glut1 transgene |
| Target | CD4 T-cell glycolysis versus lipid oxidation, and Teff versus Treg differentiation |
| Model | Mouse |
| Effect | Glycolysis supports effector subsets while lipid oxidation and AMPK activation support Treg; mTOR inhibition increases Treg only when lipid oxidation is available |
In the Atlas
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- Metformin Inhibits Hepatic mTORC1 Signaling via Dose-Dependent Mechanisms Involving AMPK and the TSC Complex (2017)
- Metformin, independent of AMPK, inhibits mTORC1 in a rag GTPase-dependent manner (2010)
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