Mechanistic target of rapamycin complex 1 is critical for invariant natural killer T-cell development and effector function.

Journal Article (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

  • PMC3939904

Electronic International Standard Serial Number (EISSN)

  • 1091-6490

Digital Object Identifier (DOI)

  • 10.1073/pnas.1315435111


  • eng

Conference Location

  • United States