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

Publication ,  Journal Article
Shin, J; Wang, S; Deng, W; Wu, J; Gao, J; Zhong, X-P
Published in: Proc Natl Acad Sci U S A
February 25, 2014

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.

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Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

February 25, 2014

Volume

111

Issue

8

Start / End Page

E776 / E783

Location

United States

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
 

Citation

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Shin, J., Wang, S., Deng, W., Wu, J., Gao, J., & Zhong, X.-P. (2014). Mechanistic target of rapamycin complex 1 is critical for invariant natural killer T-cell development and effector function. Proc Natl Acad Sci U S A, 111(8), E776–E783. https://doi.org/10.1073/pnas.1315435111
Shin, Jinwook, Shang Wang, Wenhai Deng, Jinhong Wu, Jimin Gao, and Xiao-Ping Zhong. “Mechanistic target of rapamycin complex 1 is critical for invariant natural killer T-cell development and effector function.Proc Natl Acad Sci U S A 111, no. 8 (February 25, 2014): E776–83. https://doi.org/10.1073/pnas.1315435111.
Shin J, Wang S, Deng W, Wu J, Gao J, Zhong X-P. Mechanistic target of rapamycin complex 1 is critical for invariant natural killer T-cell development and effector function. Proc Natl Acad Sci U S A. 2014 Feb 25;111(8):E776–83.
Shin, Jinwook, et al. “Mechanistic target of rapamycin complex 1 is critical for invariant natural killer T-cell development and effector function.Proc Natl Acad Sci U S A, vol. 111, no. 8, Feb. 2014, pp. E776–83. Pubmed, doi:10.1073/pnas.1315435111.
Shin J, Wang S, Deng W, Wu J, Gao J, Zhong X-P. Mechanistic target of rapamycin complex 1 is critical for invariant natural killer T-cell development and effector function. Proc Natl Acad Sci U S A. 2014 Feb 25;111(8):E776–E783.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

February 25, 2014

Volume

111

Issue

8

Start / End Page

E776 / E783

Location

United States

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