title: The effect of immunosuppressive molecules on T-cell metabolic reprogramming.
abstract: T lymphocytes undergo metabolic reprogramming to adapt to extracellular and intracellular cues. Specifically, T-cell metabolism results into ATP production, anabolism and catabolism pathways that not only support rapid cell growth and proliferation, but also differentiation and effector functions, recently referred as "immunometabolism". Quiescent naïve T cells rely on oxidative phosphorylation whereas aerobic glycolysis (Warburg effect) occurs in activated T cells (effector CD4(+) and CD8(+)). The molecular mechanisms that sense metabolic status and influence T-cell function require metabolic checkpoints including sensors of metabolic signals and transducers (Myc, HIF-1α, AMPK and mTOR). These metabolic checkpoints represent a novel therapeutic strategy for immune modulation. Interestingly, many immunosuppressive drugs including mTOR inhibitors (rapamycin), calcineurin inhibitors (tacrolimus, cyclosporine A) and inhibitors of de novo purine synthesis (6-mercaptopurine, mycophenolic acid and methotrexate) provide examples into how modulating these metabolic checkpoints can regulate T-cell activation, differentiation and function. In this Review we highlight emerging concepts about metabolic reprogramming in T-cell responses and we discuss the potential therapeutic interventions to influence T-cell fate and effector function.
authors.affiliation: INSERM UMR-S 1147, 45 rue des Saints-Pères, 75006 Paris, France; Unité Paris Descartes, Sorbonne Paris Cité, 45 rue des Saints-Pères, 75006 Paris, France. Electronic address: anafdez89@gmail.com.
authors.forename: Ana A
authors.initials: AA
authors.lastname: Fernández-Ramos
authors.affiliation: INSERM UMR-S 1147, 45 rue des Saints-Pères, 75006 Paris, France; Unité Paris Descartes, Sorbonne Paris Cité, 45 rue des Saints-Pères, 75006 Paris, France. Electronic address: virginie.poindessous@yahoo.fr.
authors.forename: Virginie
authors.initials: V
authors.lastname: Poindessous
authors.affiliation: INSERM UMR-S 1147, 45 rue des Saints-Pères, 75006 Paris, France; Unité Paris Descartes, Sorbonne Paris Cité, 45 rue des Saints-Pères, 75006 Paris, France. Electronic address: catherine.marchetti@parisdescartes.fr.
authors.forename: Catherine
authors.initials: C
authors.lastname: Marchetti-Laurent
authors.affiliation: INSERM UMR-S 1147, 45 rue des Saints-Pères, 75006 Paris, France; Unité Paris Descartes, Sorbonne Paris Cité, 45 rue des Saints-Pères, 75006 Paris, France; Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Biochimie, Pharmacogénétique et Oncologie Moléculaire, 20 rue Leblanc 75015 Paris, France. Electronic address: npallet@yahoo.fr.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Pallet
authors.affiliation: INSERM UMR-S 1147, 45 rue des Saints-Pères, 75006 Paris, France; Unité Paris Descartes, Sorbonne Paris Cité, 45 rue des Saints-Pères, 75006 Paris, France; Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Biochimie, Pharmacogénétique et Oncologie Moléculaire, 20 rue Leblanc 75015 Paris, France. Electronic address: marie-anne.loriot@parisdescartes.fr.
authors.forename: Marie-Anne
authors.initials: MA
authors.lastname: Loriot
mesh_terms: D000818:Animals; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*
chemical_list: D007166:Immunosuppressive Agents
keywords: Aerobic glycolysis; Energetic metabolism; Immunosuppressive drugs; Metabolic reprogramming; Oxidative phosphorylation; T lymphocytes