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.
Daniela MelisFortunata CarboneGiorgia MinopoliClaudia La RoccaFrancesco PernaVeronica De RosaMario GalganiGeneroso AndriaGiancarlo ParentiGiuseppe MataresePublished in: Journal of immunology (Baltimore, Md. : 1950) (2017)
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.
Keyphrases
- regulatory t cells
- end stage renal disease
- transcription factor
- dendritic cells
- newly diagnosed
- ejection fraction
- chronic kidney disease
- poor prognosis
- prognostic factors
- blood glucose
- social media
- high resolution
- type diabetes
- intellectual disability
- machine learning
- adipose tissue
- weight loss
- immune response
- mass spectrometry
- metabolic syndrome
- electronic health record
- insulin resistance
- artificial intelligence
- glycemic control