| First Author | Charbonnier LM | Year | 2019 |
| Journal | Nat Immunol | Volume | 20 |
| Issue | 9 | Pages | 1208-1219 |
| PubMed ID | 31384057 | Mgi Jnum | J:305614 |
| Mgi Id | MGI:6706652 | Doi | 10.1038/s41590-019-0442-x |
| Citation | Charbonnier LM, et al. (2019) Functional reprogramming of regulatory T cells in the absence of Foxp3. Nat Immunol 20(9):1208-1219 |
| abstractText | Regulatory T cells (Treg cells) deficient in the transcription factor Foxp3 lack suppressor function and manifest an effector T (Teff) cell-like phenotype. We demonstrate that Foxp3 deficiency dysregulates metabolic checkpoint kinase mammalian target of rapamycin (mTOR) complex 2 (mTORC2) signaling and gives rise to augmented aerobic glycolysis and oxidative phosphorylation. Specific deletion of the mTORC2 adaptor gene Rictor in Foxp3-deficient Treg cells ameliorated disease in a Foxo1 transcription factor-dependent manner. Rictor deficiency re-established a subset of Treg cell genetic circuits and suppressed the Teff cell-like glycolytic and respiratory programs, which contributed to immune dysregulation. Treatment of Treg cells from patients with FOXP3 deficiency with mTOR inhibitors similarly antagonized their Teff cell-like program and restored suppressive function. Thus, regulatory function can be re-established in Foxp3-deficient Treg cells by targeting their metabolic pathways, providing opportunities to restore tolerance in Treg cell disorders. |
