| First Author | Hawse WF | Year | 2019 |
| Journal | J Immunol | Volume | 203 |
| Issue | 11 | Pages | 2771-2775 |
| PubMed ID | 31628154 | Mgi Jnum | J:282064 |
| Mgi Id | MGI:6379961 | Doi | 10.4049/jimmunol.1900749 |
| Citation | Hawse WF, et al. (2019) Cutting Edge: TCR Signal Strength Regulates Acetyl-CoA Metabolism via AKT. J Immunol 203(11):2771-2775 |
| abstractText | TCR signaling activates kinases including AKT/mTOR that engage metabolic networks to support the energetic demands of a T cell during an immune response. It is realized that CD4(+) T cell subsets have different metabolic requirements. Yet, how TCR signaling is coupled to the regulation of intermediate metabolites and how changes in metabolite flux contribute to T cell differentiation are less established. We find that TCR signaling regulates acetyl-CoA metabolism via AKT in murine CD4(+) T cells. Weak TCR signals promote AKT-catalyzed phosphorylation and inhibition of citrate synthase, elevated acetyl-CoA levels, and hyperacetylation of mitochondrial proteins. Genetic knockdown of citrate synthase promotes increased nuclear acetyl-CoA levels, increased histone acetylation at the FOXP3 promotor and induction of FOXP3 transcription. These data identify a circuit between AKT signaling and acetyl-CoA metabolism regulated via TCR signal strength and that transient fluctuations in acetyl-CoA levels function in T cell fate decisions. |
