title: The Proteomic Landscape of Human Ex Vivo Regulatory and Conventional T Cells Reveals Specific Metabolic Requirements.
abstract: Human CD4(+)CD25(hi)Foxp3(+)CD127(-) Treg and CD4(+)CD25(-)Foxp3(-) Tconv cell functions are governed by their metabolic requirements. Here we report a comprehensive comparative analysis between ex vivo human Treg and Tconv cells that comprises analyses of the proteomic networks in subcellular compartments. We identified a dominant proteomic signature at the metabolic level that primarily impacted the highly-tuned balance between glucose and fatty-acid oxidation in the two cell types. Ex vivo Treg cells were highly glycolytic while Tconv cells used predominantly fatty-acid oxidation (FAO). When cultured in vitro, Treg cells engaged both glycolysis and FAO to proliferate, while Tconv cell proliferation mainly relied on glucose metabolism. Our unbiased proteomic analysis provides a molecular picture of the impact of metabolism on ex vivo human Treg versus Tconv cell functions that might be relevant for therapeutic manipulations of these cells.
authors.affiliation: Laboratorio di Immunologia, Istituto di Endocrinologia e Oncologia Sperimentale, Consiglio Nazionale delle Ricerche (IEOS-CNR), 80131 Napoli, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Procaccini
authors.affiliation: Laboratorio di Immunologia, Istituto di Endocrinologia e Oncologia Sperimentale, Consiglio Nazionale delle Ricerche (IEOS-CNR), 80131 Napoli, Italy.
authors.forename: Fortunata
authors.initials: F
authors.lastname: Carbone
authors.affiliation: Istituto di Tecnologie Biomediche, Consiglio Nazionale delle Ricerche (ITB-CNR), 20090 Segrate, Milano, Italy.
authors.forename: Dario
authors.initials: D
authors.lastname: Di Silvestre
authors.affiliation: Istituto di Tecnologie Biomediche, Consiglio Nazionale delle Ricerche (ITB-CNR), 20090 Segrate, Milano, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Brambilla
authors.affiliation: Laboratorio di Immunologia, Istituto di Endocrinologia e Oncologia Sperimentale, Consiglio Nazionale delle Ricerche (IEOS-CNR), 80131 Napoli, Italy; Unità di NeuroImmunologia, IRCCS Fondazione Santa Lucia, 00143 Roma, Italy.
authors.forename: Veronica
authors.initials: V
authors.lastname: De Rosa
authors.affiliation: Laboratorio di Immunologia, Istituto di Endocrinologia e Oncologia Sperimentale, Consiglio Nazionale delle Ricerche (IEOS-CNR), 80131 Napoli, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Galgani
authors.affiliation: Dipartimento di Scienze Mediche Traslazionali e Centro Interdipartimentale di Ricerca in Scienze Immunologiche di Base Cliniche (CISI), Università di Napoli "Federico II," 80131 Napoli, Italy.
authors.forename: Deriggio
authors.initials: D
authors.lastname: Faicchia
authors.affiliation: Dipartimento di Scienze Mediche Traslazionali e Centro Interdipartimentale di Ricerca in Scienze Immunologiche di Base Cliniche (CISI), Università di Napoli "Federico II," 80131 Napoli, Italy.
authors.forename: Gianni
authors.initials: G
authors.lastname: Marone
authors.affiliation: Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università di Napoli "Federico II," 80131 Napoli, Italy.
authors.forename: Donatella
authors.initials: D
authors.lastname: Tramontano
authors.affiliation: Istituto di Genetica e Biofisica "A. Buzzati-Traverso" Consiglio Nazionale delle Ricerche (IGB-CNR), 80131 Napoli, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Corona
authors.affiliation: Dipartimento di Neuroscienze e Scienze Riproduttive e Odontostomatologiche, Università di Napoli "Federico II," 80131 Napoli, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Alviggi
authors.affiliation: Dipartimento di Biologia, Complesso Universitario di Monte Sant'Angelo, Università di Napoli ''Federico II'', Napoli 80126, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Porcellini
authors.affiliation: Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Antonio
authors.initials: A
authors.lastname: La Cava
authors.affiliation: Istituto di Tecnologie Biomediche, Consiglio Nazionale delle Ricerche (ITB-CNR), 20090 Segrate, Milano, Italy; Istituto di Scienze della Vita, Scuola Superiore Sant'Anna, 56127 Pisa, Italy.
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Mauri
authors.affiliation: Laboratorio di Immunologia, Istituto di Endocrinologia e Oncologia Sperimentale, Consiglio Nazionale delle Ricerche (IEOS-CNR), 80131 Napoli, Italy; Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università di Napoli "Federico II," 80131 Napoli, Italy. Electronic address: giuseppe.matarese@unina.it.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Matarese
mesh_terms: D015704:CD4 Antigens / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D005227:Fatty Acids / Q000378:metabolism*; D051858:Forkhead Transcription Factors / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D006019:Glycolysis; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D010084:Oxidation-Reduction; D040901:Proteomics; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D059467:Transcriptome
chemical_list: D015704:CD4 Antigens; C418974:FOXP3 protein, human; D005227:Fatty Acids; D051858:Forkhead Transcription Factors; D053645:Interleukin-2 Receptor alpha Subunit; D005947:Glucose
keywords: Conventional T cells; Immune Tolerance; Metabolism; Proteomic Analysis; Regulatory T cells