title: Cutting Edge: Increased Autoimmunity Risk in Glycogen Storage Disease Type 1b Is Associated with a Reduced Engagement of Glycolysis in T Cells and an Impaired Regulatory T Cell Function.
abstract: Glycogen storage disease type 1b (GSD-1b) is an autosomal-recessive disease caused by mutation of glucose-6-phosphate transporter and characterized by altered glycogen/glucose homeostasis. A higher frequency of autoimmune diseases has been observed in GSD-1b patients, but the molecular determinants leading to this phenomenon remain unknown. To address this question, we investigated the effect of glucose-6-phosphate transporter mutation on immune cell homeostasis and CD4+T cell functions. In GSD-1b subjects, we found lymphopenia and a reduced capacity of T cells to engage glycolysis upon TCR stimulation. These phenomena associated with reduced expression of the FOXP3 transcription factor, lower suppressive function in peripheral CD4+CD25+FOXP3+regulatory T cells, and an impaired capacity of CD4+CD25-conventional T cells to induce expression of FOXP3 after suboptimal TCR stimulation. These data unveil the metabolic determinant leading to an increased autoimmunity risk in GSD-1b patients.
authors.affiliation: Sezione di Pediatria, Dipartimento di Scienze Mediche Traslazionali, Università degli Studi di Napoli "Federico II," 80131 Naples, Italy; giuseppe.matarese@unina.it daniela.melis@unina.it.
authors.forename: Daniela
authors.identifier: 0000-0002-9458-3926
authors.initials: D
authors.lastname: Melis
authors.affiliation: Laboratorio di Immunologia, Istituto di Endocrinologia e Oncologia Sperimentale, Consiglio Nazionale delle Ricerche, 80131 Naples, Italy.
authors.forename: Fortunata
authors.initials: F
authors.lastname: Carbone
authors.affiliation: Sezione di Pediatria, Dipartimento di Scienze Mediche Traslazionali, Università degli Studi di Napoli "Federico II," 80131 Naples, Italy.
authors.forename: Giorgia
authors.initials: G
authors.lastname: Minopoli
authors.affiliation: Laboratorio di Immunologia, Istituto di Endocrinologia e Oncologia Sperimentale, Consiglio Nazionale delle Ricerche, 80131 Naples, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: La Rocca
authors.affiliation: Dipartimento di Medicina Clinica e Chirurgia, Università degli Studi di Napoli "Federico II," 80131 Naples, Italy.
authors.forename: Francesco
authors.identifier: 0000-0001-5319-0977
authors.initials: F
authors.lastname: Perna
authors.affiliation: Laboratorio di Immunologia, Istituto di Endocrinologia e Oncologia Sperimentale, Consiglio Nazionale delle Ricerche, 80131 Naples, Italy.
authors.forename: Veronica
authors.identifier: 0000-0002-9477-0991
authors.initials: V
authors.lastname: De Rosa
authors.affiliation: Laboratorio di Immunologia, Istituto di Endocrinologia e Oncologia Sperimentale, Consiglio Nazionale delle Ricerche, 80131 Naples, Italy.
authors.forename: Mario
authors.identifier: 0000-0001-8414-1676
authors.initials: M
authors.lastname: Galgani
authors.affiliation: Sezione di Pediatria, Dipartimento di Scienze Mediche Traslazionali, Università degli Studi di Napoli "Federico II," 80131 Naples, Italy.
authors.forename: Generoso
authors.initials: G
authors.lastname: Andria
authors.affiliation: Sezione di Pediatria, Dipartimento di Scienze Mediche Traslazionali, Università degli Studi di Napoli "Federico II," 80131 Naples, Italy.|Istituto Telethon di Genetica e Medicina, 80078 Pozzuoli, Naples, Italy; and.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Parenti
authors.affiliation: Laboratorio di Immunologia, Istituto di Endocrinologia e Oncologia Sperimentale, Consiglio Nazionale delle Ricerche, 80131 Naples, Italy; giuseppe.matarese@unina.it daniela.melis@unina.it.|Laboratorio delle Cellule T Regolatorie, Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli "Federico II," 80131 Naples, Italy.
authors.forename: Giuseppe
authors.identifier: 0000-0001-9429-0616
authors.initials: G
authors.lastname: Matarese
mesh_terms: D000293:Adolescent; D000328:Adult; D017920:Antiporters / Q000235:genetics / Q000378:metabolism; D015551:Autoimmunity; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D005953:Glycogen Storage Disease Type I / Q000276:immunology* / Q000378:metabolism* / Q000503:physiopathology; D006019:Glycolysis; D006706:Homeostasis; D006801:Humans; D007223:Infant; D008231:Lymphopenia / Q000276:immunology / Q000503:physiopathology; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D055815:Young Adult
chemical_list: D017920:Antiporters; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D009004:Monosaccharide Transport Proteins; D011948:Receptors, Antigen, T-Cell; C111261:glucose 6-phosphate(transporter)