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Metabolic regulation of T cell development by Sin1-mTORC2 is mediated by pyruvate kinase M2

Xinxing Ouyang1, Yuheng Han1, Guojun Qu1

  • 1Shanghai Institute of Immunology, Department of Immunology and Microbiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Journal of Molecular Cell Biology
|November 15, 2018
PubMed

Insights

The mammalian target of rapamycin complex 2 (mTORC2) pathway regulates early T cell development by controlling glucose metabolism. This study identifies a novel mTORC2-PKM2 signaling axis crucial for thymocyte proliferation and development.

Area of Science:

  • Immunology
  • Cell Metabolism
  • Molecular Biology

Background:

  • Glucose metabolism is vital for thymocyte development.
  • The role of mTORC2 in early thymocyte metabolism and development is not fully understood.

Purpose of the Study:

  • To investigate the role of Sin1-mTORC2 in early thymocyte development and metabolism.
  • To identify key effectors and molecular mechanisms regulated by mTORC2 in thymocytes.

Main Methods:

  • Genetic ablation of Sin1 in T lineage cells.
  • Analysis of thymocyte development, proliferation, and glycolysis.
  • Molecular studies involving PKM2 expression, AKT signaling, and PPAR-γ translocation.

Main Results:

  • Genetic deletion of Sin1 impairs thymocyte development at the double-negative (DN) stage.
  • Sin1-deficient DN thymocytes exhibit reduced proliferation and glycolysis.
  • PKM2 is identified as a critical Sin1 effector, and its expression is regulated by AKT-dependent PPAR-γ nuclear translocation.

Conclusions:

  • The study uncovers a novel mTORC2-PPAR-γ-PKM2 pathway essential for immune-metabolic regulation during early thymocyte development.
  • This pathway highlights a new mechanism linking cell metabolism to immune cell development.
Keywords:
PKM2PPAR-γSin1mTORC2metabolismthymocyte development

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