| First Author | Luda KM | Year | 2023 |
| Journal | Immunity | Volume | 56 |
| Issue | 9 | Pages | 2021-2035.e8 |
| PubMed ID | 37516105 | Mgi Jnum | J:339932 |
| Mgi Id | MGI:7525108 | Doi | 10.1016/j.immuni.2023.07.002 |
| Citation | Luda KM, et al. (2023) Ketolysis drives CD8(+) T cell effector function through effects on histone acetylation. Immunity |
| abstractText | Environmental nutrient availability influences T cell metabolism, impacting T cell function and shaping immune outcomes. Here, we identified ketone bodies (KBs)-including beta-hydroxybutyrate (betaOHB) and acetoacetate (AcAc)-as essential fuels supporting CD8(+) T cell metabolism and effector function. betaOHB directly increased CD8(+) T effector (Teff) cell cytokine production and cytolytic activity, and KB oxidation (ketolysis) was required for Teff cell responses to bacterial infection and tumor challenge. CD8(+) Teff cells preferentially used KBs over glucose to fuel the tricarboxylic acid (TCA) cycle in vitro and in vivo. KBs directly boosted the respiratory capacity and TCA cycle-dependent metabolic pathways that fuel CD8(+) T cell function. Mechanistically, betaOHB was a major substrate for acetyl-CoA production in CD8(+) T cells and regulated effector responses through effects on histone acetylation. Together, our results identify cell-intrinsic ketolysis as a metabolic and epigenetic driver of optimal CD8(+) T cell effector responses. |
