Mechanistic target of rapamycin complex 1 is critical for invariant natural killer T-cell development and effector function.
The mechanisms that control invariant natural killer T (iNKT)-cell development and function are still poorly understood. The mechanistic or mammalian target of rapamycin (mTOR) integrates various environmental signals/cues to regulate cell growth, proliferation, metabolism, and survival. We report here that ablation of mTOR complex 1 (mTORC1) signaling by conditionally deleting Raptor causes severe defects in iNKT-cell development at early stages, leading to drastic reductions in iNKT-cell numbers in the thymus and periphery. In addition, loss of Raptor impairs iNKT-cell proliferation and production of cytokines upon α-galactosylceramide stimulation in vitro and in vivo, and inhibits liver inflammation in an iNKT cell-mediated hepatitis model. Furthermore, Raptor deficiency and rapamycin treatment lead to aberrant intracellular localization and functional impairment of promyelocytic leukemia zinc-finger, a transcription factor critical for iNKT-cell development and effector programs. Our findings define an essential role of mTORC1 to direct iNKT-cell lineage development and effector function.
Duke Scholars
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- Thymocytes
- TOR Serine-Threonine Kinases
- Statistics, Nonparametric
- Real-Time Polymerase Chain Reaction
- Promyelocytic Leukemia Zinc Finger Protein
- Natural Killer T-Cells
- Multiprotein Complexes
- Microscopy, Fluorescence
- Mice, Knockout
- Mice
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Thymocytes
- TOR Serine-Threonine Kinases
- Statistics, Nonparametric
- Real-Time Polymerase Chain Reaction
- Promyelocytic Leukemia Zinc Finger Protein
- Natural Killer T-Cells
- Multiprotein Complexes
- Microscopy, Fluorescence
- Mice, Knockout
- Mice