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The TSC-mTOR pathway regulates macrophage polarization

Author

Listed:
  • Vanessa Byles

    (Harvard School of Public Health)

  • Anthony J. Covarrubias

    (Harvard School of Public Health)

  • Issam Ben-Sahra

    (Harvard School of Public Health)

  • Dudley W. Lamming

    (Whitehead Institute for Biomedical Research
    MIT
    Howard Hughes Medical Institute, MIT
    Broad Institute of Harvard and MIT, Seven Cambridge Center)

  • David M. Sabatini

    (Whitehead Institute for Biomedical Research
    MIT
    Howard Hughes Medical Institute, MIT
    Broad Institute of Harvard and MIT, Seven Cambridge Center)

  • Brendan D. Manning

    (Harvard School of Public Health)

  • Tiffany Horng

    (Harvard School of Public Health)

Abstract

Macrophages are able to polarize to proinflammatory M1 or alternative M2 states with distinct phenotypes and physiological functions. How metabolic status regulates macrophage polarization remains not well understood, and here we examine the role of mTOR (mechanistic target of rapamycin), a central metabolic pathway that couples nutrient sensing to regulation of metabolic processes. Using a mouse model in which myeloid lineage-specific deletion of Tsc1 (Tsc1Δ/Δ) leads to constitutive mTOR complex 1 (mTORC1) activation, we find that Tsc1Δ/Δ macrophages are refractory to IL-4-induced M2 polarization, but produce increased inflammatory responses to proinflammatory stimuli. Moreover, mTORC1-mediated downregulation of Akt signalling critically contributes to defective polarization. These findings highlight a key role for the mTOR pathway in regulating macrophage polarization, and suggest how nutrient sensing and metabolic status could be ‘hard-wired’ to control of macrophage function, with broad implications for regulation of type 2 immunity, inflammation and allergy.

Suggested Citation

  • Vanessa Byles & Anthony J. Covarrubias & Issam Ben-Sahra & Dudley W. Lamming & David M. Sabatini & Brendan D. Manning & Tiffany Horng, 2013. "The TSC-mTOR pathway regulates macrophage polarization," Nature Communications, Nature, vol. 4(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms3834
    DOI: 10.1038/ncomms3834
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    Cited by:

    1. Weiyuan Li & Lu Pan & Weifeng Hong & Florent Ginhoux & Xuan Zhang & Chunjie Xiao & Xuexin Li, 2024. "A single-cell pan-cancer analysis to show the variability of tumor-infiltrating myeloid cells in immune checkpoint blockade," Nature Communications, Nature, vol. 15(1), pages 1-13, December.

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