title: Fatty acid metabolic reprogramming via mTOR-mediated inductions of PPARγ directs early activation of T cells.
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.
authors.affiliation: Department of Immunology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana Chuo-ku, Chiba 260-8670, Japan.
authors.forename: Mulki
authors.initials: M
authors.lastname: Angela
authors.affiliation: Department of Immunology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana Chuo-ku, Chiba 260-8670, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Endo
authors.affiliation: Department of Immunology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana Chuo-ku, Chiba 260-8670, Japan.
authors.forename: Hikari K
authors.initials: HK
authors.lastname: Asou
authors.affiliation: Department of Immunology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana Chuo-ku, Chiba 260-8670, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yamamoto
authors.affiliation: Department of Immunology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana Chuo-ku, Chiba 260-8670, Japan.|South Australian Health and Medical Research Institute, North Terrace, Adelaide South Australia 5000, Australia.
authors.forename: Damon J
authors.identifier: 0000-0001-5709-857X
authors.initials: DJ
authors.lastname: Tumes
authors.affiliation: Department of Clinical Cell Biology and Medicine, Graduate School of Medicine, Chiba University, 1-8-1 Inohana Chuo-ku, Chiba 260-8670, Japan.
authors.forename: Hirotake
authors.initials: H
authors.lastname: Tokuyama
authors.affiliation: Department of Clinical Cell Biology and Medicine, Graduate School of Medicine, Chiba University, 1-8-1 Inohana Chuo-ku, Chiba 260-8670, Japan.
authors.forename: Koutaro
authors.initials: K
authors.lastname: Yokote
authors.affiliation: Department of Immunology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana Chuo-ku, Chiba 260-8670, Japan.|AMED-CREST, AMED, 1-8-1 Inohana Chuo-ku, Chiba 260-8670, Japan.
authors.forename: Toshinori
authors.initials: T
authors.lastname: Nakayama
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D047369:Chromatin Immunoprecipitation; D005227:Fatty Acids / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D064368:Healthy Volunteers; D006801:Humans; D008213:Lymphocyte Activation / Q000502:physiology*; D000076222:Mechanistic Target of Rapamycin Complex 1 / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D047495:PPAR gamma / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D058570:TOR Serine-Threonine Kinases; D015854:Up-Regulation / Q000502:physiology
chemical_list: D005227:Fatty Acids; D047495:PPAR gamma; D034741:RNA, Small Interfering; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases