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Fatty acid metabolic reprogramming via mTOR-mediated inductions of PPARγ directs early activation of T cells

Author

Listed:
  • Mulki Angela

    (Graduate School of Medicine, Chiba University)

  • Yusuke Endo

    (Graduate School of Medicine, Chiba University)

  • Hikari K. Asou

    (Graduate School of Medicine, Chiba University)

  • Takeshi Yamamoto

    (Graduate School of Medicine, Chiba University)

  • Damon J. Tumes

    (Graduate School of Medicine, Chiba University
    South Australian Health and Medical Research Institute, North Terrace)

  • Hirotake Tokuyama

    (Graduate School of Medicine, Chiba University)

  • Koutaro Yokote

    (Graduate School of Medicine, Chiba University)

  • Toshinori Nakayama

    (Graduate School of Medicine, Chiba University
    AMED-CREST, AMED)

Abstract

To fulfil the bioenergetic requirements for increased cell size and clonal expansion, activated T cells reprogramme their metabolic signatures from energetically quiescent to activated. However, the molecular mechanisms and essential components controlling metabolic reprogramming in T cells are not well understood. Here, we show that the mTORC1–PPARγ pathway is crucial for the fatty acid uptake programme in activated CD4+ T cells. This pathway is required for full activation and rapid proliferation of naive and memory CD4+ T cells. PPARγ directly binds and induces genes associated with fatty acid uptake in CD4+ T cells in both mice and humans. The PPARγ-dependent fatty acid uptake programme is critical for metabolic reprogramming. Thus, we provide important mechanistic insights into the metabolic reprogramming mechanisms that govern the expression of key enzymes, fatty acid metabolism and the acquisition of an activated phenotype during CD4+ T cell activation.

Suggested Citation

  • Mulki Angela & Yusuke Endo & Hikari K. Asou & Takeshi Yamamoto & Damon J. Tumes & Hirotake Tokuyama & Koutaro Yokote & Toshinori Nakayama, 2016. "Fatty acid metabolic reprogramming via mTOR-mediated inductions of PPARγ directs early activation of T cells," Nature Communications, Nature, vol. 7(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms13683
    DOI: 10.1038/ncomms13683
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    Cited by:

    1. Nicole L. Bertschi & Oliver Steck & Fabian Luther & Cecilia Bazzini & Leonhard Meyenn & Stefanie Schärli & Angela Vallone & Andrea Felser & Irene Keller & Olivier Friedli & Stefan Freigang & Nadja Beg, 2023. "PPAR-γ regulates the effector function of human T helper 9 cells by promoting glycolysis," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    2. Luca Simula & Mattia Fumagalli & Lene Vimeux & Irena Rajnpreht & Philippe Icard & Gary Birsen & Dongjie An & Frédéric Pendino & Adrien Rouault & Nadège Bercovici & Diane Damotte & Audrey Lupo-Mansuet , 2024. "Mitochondrial metabolism sustains CD8+ T cell migration for an efficient infiltration into solid tumors," Nature Communications, Nature, vol. 15(1), pages 1-23, December.

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