| First Author | Yang K | Year | 2018 |
| Journal | Sci Immunol | Volume | 3 |
| Issue | 25 | PubMed ID | 29980617 |
| Mgi Jnum | J:370115 | Mgi Id | MGI:8188394 |
| Doi | 10.1126/sciimmunol.aas9818 | Citation | Yang K, et al. (2018) Metabolic signaling directs the reciprocal lineage decisions of alphabeta and gammadelta T cells. Sci Immunol 3(25) |
| abstractText | The interaction between extrinsic factors and intrinsic signal strength governs thymocyte development, but the mechanisms linking them remain elusive. We report that mechanistic target of rapamycin complex 1 (mTORC1) couples microenvironmental cues with metabolic programs to orchestrate the reciprocal development of two fundamentally distinct T cell lineages, the alphabeta and gammadelta T cells. Developing thymocytes dynamically engage metabolic programs including glycolysis and oxidative phosphorylation, as well as mTORC1 signaling. Loss of RAPTOR-mediated mTORC1 activity impairs the development of alphabeta T cells but promotes gammadelta T cell generation, associated with disrupted metabolic remodeling of oxidative and glycolytic metabolism. Mechanistically, we identify mTORC1-dependent control of reactive oxygen species production as a key metabolic signal in mediating alphabeta and gammadelta T cell development, and perturbation of redox homeostasis impinges upon thymocyte fate decisions and mTORC1-associated phenotypes. Furthermore, single-cell RNA sequencing and genetic dissection reveal that mTORC1 links developmental signals from T cell receptors and NOTCH to coordinate metabolic activity and signal strength. Our results establish mTORC1-driven metabolic signaling as a decisive factor for reciprocal alphabeta and gammadelta T cell development and provide insight into metabolic control of cell signaling and fate decisions. |
