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Updated: Feb 2, 2026

Flow Cytometry-based Assay for the Monitoring of NK Cell Functions
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Crosstalks between mTORC1 and mTORC2 variagate cytokine signaling to control NK maturation and effector function

Fangjie Wang1, Meng Meng1, Banghui Mo1

  • 1Institute of Materia Medica, College of Pharmacy, Army Medical University (Third Military Medical University), 30# Gaotanyan Road, Shapingba District, Chongqing, 400038, China.

Nature Communications
|November 20, 2018
PubMed

Insights

The mechanistic target of rapamycin (mTOR) pathway, specifically mTORC1 and mTORC2, is crucial for natural killer (NK) cell maturation and function. These pathways cooperatively regulate NK cell development and effector functions.

Area of Science:

  • Immunology
  • Cellular Metabolism
  • Molecular Biology

Background:

  • The mechanistic/mammalian target of rapamycin (mTOR) kinase is a key regulator of cellular processes.
  • Its role in natural killer (NK) cell development and function is not fully understood.
  • mTOR exists in two complexes, mTORC1 and mTORC2, with distinct functions.

Purpose of the Study:

  • To elucidate the specific roles of mTORC1 and mTORC2 in NK cell maturation and function.
  • To investigate the cooperative and non-redundant mechanisms governing NK cell development.
  • To understand the opposing effects of mTORC1 and mTORC2 on NK cell effector functions and metabolism.

Main Methods:

  • Conditional deletion of Raptor (mTORC1) and Rictor (mTORC2) in NK cells.
  • Analysis of NK cell maturation markers, including Tbx21 and Eomes expression.
  • Assessment of NK cell cytolytic function and metabolic activity.
  • Investigation of signaling crosstalk between mTORC1 and mTORC2 via IL-15/STAT5 pathways.

Main Results:

  • mTORC1 and mTORC2 cooperatively and non-redundantly promote NK cell maturation by controlling Tbx21 and Eomes expression.
  • mTORC1 enhances anti-tumor cytolytic function, while mTORC2 inhibits it.
  • mTORC1 and mTORC2 exhibit opposing effects on NK cell metabolism.
  • mTORC1 sustains mTORC2 activity via IL-15 signaling; mTORC2 represses mTORC1-mediated effector functions by regulating SLC7A5 expression.

Conclusions:

  • mTORC1 and mTORC2 signaling pathways play critical, distinct, and cooperative roles in regulating NK cell maturation and effector functions.
  • The intricate crosstalk between mTORC1 and mTORC2 modulates NK cell activation kinetics and magnitude.
  • This study defines a new paradigm for understanding NK cell modulation by the mTOR pathway.

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