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A Novel Feeder-free System for Mass Production of Murine Natural Killer Cells In Vitro
10:36

A Novel Feeder-free System for Mass Production of Murine Natural Killer Cells In Vitro

Published on: January 9, 2018

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mTORC1 and mTORC2 differentially promote natural killer cell development

Chao Yang1,2, Shirng-Wern Tsaih3,4, Angela Lemke3,4

  • 1Laboratory of Molecular Immunology and Immunotherapy, Blood Research Institute, Blood Center of Wisconsin, Milwaukee, United States.

Elife
|May 30, 2018
PubMed

Insights

Mechanistic target of rapamycin complex 1 (mTORC1) and mTOR complex 2 (mTORC2) have distinct roles in natural killer (NK) cell development. mTORC1 regulates early NK cell development, while mTORC2 controls terminal maturation.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • Natural killer (NK) cells are crucial innate lymphoid cells for immunity.
  • The mechanistic target of rapamycin (mTOR) pathway is vital for NK cell development, but the specific roles of its complexes (mTORC1 and mTORC2) are unclear.

Purpose of the Study:

  • To elucidate the independent functions of mTORC1 and mTORC2 in regulating natural killer (NK) cell development and maturation.

Main Methods:

  • Utilized conditional knockout (cKO) mouse models with Ncr1-mediated deletion of Rptor (mTORC1 component) or Rictor (mTORC2 component).
  • Analyzed NK cell populations, gene expression profiles, and key signaling pathways (e.g., Akt, FoxO1, T-bet).

Main Results:

  • Deletion of Rptor impaired NK cell transition from CD27+CD11b- to CD27+CD11b+ stages.
  • Rictor deletion compromised terminal maturation from CD27+CD11b+ to CD27-CD11b+ stages.
  • Raptor deficiency caused broad gene expression changes, while Rictor loss had more restricted effects, including reduced T-bet expression linked to impaired mTORC2-Akt-FoxO1 signaling.

Conclusions:

  • mTORC1 and mTORC2 play divergent and stage-specific roles in NK cell development.
  • mTORC1 is critical for early NK cell development, whereas mTORC2 regulates terminal maturation through specific signaling pathways.
Keywords:
NK cellsRaptorRictorimmunologyinflammationmouse

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