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.

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 / Melis, Daniela; Carbone, Fortunata; Minopoli, Giorgia; La Rocca, Claudia; Perna, Francesco; De Rosa, Veronica; Galgani, Mario; Andria, Generoso; Parenti, Giancarlo; Matarese, Giuseppe. - In: JOURNAL OF IMMUNOLOGY. - ISSN 0022-1767. - 198:10(2017), pp. 3803-3808. [10.4049/jimmunol.1601946]

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

Melis, Daniela;Carbone, Fortunata;MINOPOLI, GIORGIA;La Rocca, Claudia;Perna, Francesco;De Rosa, Veronica;Galgani, Mario;Andria, Generoso;Parenti, Giancarlo;Matarese, Giuseppe
2017

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.
2017
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 / Melis, Daniela; Carbone, Fortunata; Minopoli, Giorgia; La Rocca, Claudia; Perna, Francesco; De Rosa, Veronica; Galgani, Mario; Andria, Generoso; Parenti, Giancarlo; Matarese, Giuseppe. - In: JOURNAL OF IMMUNOLOGY. - ISSN 0022-1767. - 198:10(2017), pp. 3803-3808. [10.4049/jimmunol.1601946]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/701028
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