< Terug naar vorige pagina

Publicatie

Functional reprogramming of regulatory T cells in the absence of Foxp3

Tijdschriftbijdrage - Tijdschriftartikel

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.
Tijdschrift: Nature Immunology
ISSN: 1529-2908
Issue: 9
Volume: 20
Pagina's: 1208 - +
Jaar van publicatie:2019
BOF-keylabel:ja
IOF-keylabel:ja
BOF-publication weight:10
CSS-citation score:4
Auteurs:International
Authors from:Higher Education
Toegankelijkheid:Closed