Other
16 Authors
- Wang Y,
- Hu X,
- Zhang HG,
- Rouchka EC,
- Qin H,
- Chen X,
- Montoya-Durango DE,
- Chariker JH,
- Cai Y,
- Sarojini H,
- Zheng J,
- Li H,
- Qiu F,
- Chien S,
- Yan J,
- Ding C
| First Author | Wang Y | Year | 2023 |
| Journal | iScience | Volume | 26 |
| Issue | 5 | Pages | 106630 |
| PubMed ID | 37192973 | Mgi Jnum | J:359142 |
| Mgi Id | MGI:7483950 | Doi | 10.1016/j.isci.2023.106630 |
| Citation | Wang Y, et al. (2023) Natural gammadeltaT17 cell development and functional acquisition is governed by the mTORC2-c-Maf-controlled mitochondrial fission pathway. iScience 26(5):106630 |
| abstractText | Natural IL-17-producing gammadelta T cells (gammadeltaT17 cells) are unconventional innate-like T cells that undergo functional programming in the fetal thymus. However, the intrinsic metabolic mechanisms of gammadeltaT17 cell development remain undefined. Here, we demonstrate that mTORC2, not mTORC1, selectively controls the functional fate commitment of gammadeltaT17 cells through regulating transcription factor c-Maf expression. scRNA-seq data suggest that fetal and adult gammadeltaT17 cells predominately utilize mitochondrial metabolism. mTORC2 deficiency results in impaired Drp1-mediated mitochondrial fission and mitochondrial dysfunction characterized by mitochondrial membrane potential (DeltaPsim) loss, reduced oxidative phosphorylation (OXPHOS), and subsequent ATP depletion. Treatment with the Drp1 inhibitor Mdivi-1 alleviates imiquimod-induced skin inflammation. Reconstitution of intracellular ATP levels by ATP-encapsulated liposome completely rescues gammadeltaT17 defect caused by mTORC2 deficiency, revealing the fundamental role of metabolite ATP in gammadeltaT17 development. These results provide an in-depth insight into the intrinsic link between the mitochondrial OXPHOS pathway and gammadeltaT17 thymic programming and functional acquisition. |
