Mechanistic target of rapamycin complex 1 is critical for invariant natural killer T-cell development and effector function.
Published
Journal Article
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.
Full Text
Duke Authors
Cited Authors
- Shin, J; Wang, S; Deng, W; Wu, J; Gao, J; Zhong, X-P
Published Date
- February 25, 2014
Published In
Volume / Issue
- 111 / 8
Start / End Page
- E776 - E783
PubMed ID
- 24516149
Pubmed Central ID
- 24516149
Electronic International Standard Serial Number (EISSN)
- 1091-6490
Digital Object Identifier (DOI)
- 10.1073/pnas.1315435111
Language
- eng
Conference Location
- United States