| First Author | Shi LZ | Year | 2011 |
| Journal | J Exp Med | Volume | 208 |
| Issue | 7 | Pages | 1367-76 |
| PubMed ID | 21708926 | Mgi Jnum | J:176809 |
| Mgi Id | MGI:5292778 | Doi | 10.1084/jem.20110278 |
| Citation | Shi LZ, et al. (2011) HIF1alpha-dependent glycolytic pathway orchestrates a metabolic checkpoint for the differentiation of TH17 and Treg cells. J Exp Med 208(7):1367-76 |
| abstractText | Upon antigen stimulation, the bioenergetic demands of T cells increase dramatically over the resting state. Although a role for the metabolic switch to glycolysis has been suggested to support increased anabolic activities and facilitate T cell growth and proliferation, whether cellular metabolism controls T cell lineage choices remains poorly understood. We report that the glycolytic pathway is actively regulated during the differentiation of inflammatory T(H)17 and Foxp3-expressing regulatory T cells (T(reg) cells) and controls cell fate determination. T(H)17 but not T(reg) cell-inducing conditions resulted in strong up-regulation of the glycolytic activity and induction of glycolytic enzymes. Blocking glycolysis inhibited T(H)17 development while promoting T(reg) cell generation. Moreover, the transcription factor hypoxia-inducible factor 1alpha (HIF1alpha) was selectively expressed in T(H)17 cells and its induction required signaling through mTOR, a central regulator of cellular metabolism. HIF1alpha-dependent transcriptional program was important for mediating glycolytic activity, thereby contributing to the lineage choices between T(H)17 and T(reg) cells. Lack of HIF1alpha resulted in diminished T(H)17 development but enhanced T(reg) cell differentiation and protected mice from autoimmune neuroinflammation. Our studies demonstrate that HIF1alpha-dependent glycolytic pathway orchestrates a metabolic checkpoint for the differentiation of T(H)17 and T(reg) cells. |
