Immunometabolic profiling of T cells from .. relapsing-remitting [MS] .. impairment in glycolysis and mitochondrial respiration, 2017, Matarese et al

Andy · Oct 15, 2020

Full title: Immunometabolic profiling of T cells from patients with relapsing-remitting multiple sclerosis reveals an impairment in glycolysis and mitochondrial respiration

Metabolic reprogramming is shaped to support specific cell functions since cellular metabolism controls the final outcome of immune response. Multiple sclerosis (MS) is an autoimmune disease resulting from loss of immune tolerance against central nervous system (CNS) myelin. Metabolic alterations of T cells occurring during MS are not yet well understood and their studies could have relevance in the comprehension of the pathogenetic events leading to loss of immune tolerance to self and to develop novel therapeutic strategies aimed at limiting MS progression.

Methods and Results
In this report, we observed that extracellular acidification rate (ECAR) and oxygen consumption rate (OCR), indicators of glycolysis and oxidative phosphorylation, respectively, were impaired during T cell activation in naïve-to-treatment relapsing remitting (RR)MS patients when compared with healthy controls. These results were also corroborated at biochemical level by a reduced expression of the glycolitic enzymes aldolase, enolase 1, hexokinase I, and by reduction of Krebs cycle enzymes dihydrolipoamide-S-acetyl transferase (DLAT) and dihydrolipoamide-S-succinyl transferase (DLST). Treatment of RRMS patients with interferon beta-1a (IFN beta-1a) was able to restore T cell glycolysis and mitochondrial respiration as well as the amount of the metabolic enzymes to a level comparable to that of healthy controls. These changes associated with an up-regulation of the glucose transporter-1 (GLUT-1), a key element in intracellular transport of glucose.

Conclusions
Our data suggest that T cells from RRMS patients display a reduced engagement of glycolysis and mitochondrial respiration, reversible upon IFN beta-1a treatment, thus suggesting an involvement of an altered metabolism in the pathogenesis of MS.
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Open access, https://www.metabolismjournal.com/article/S0026-0495(17)30217-2/fulltext

Mij · Oct 15, 2020

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex disease with no known cause or mechanism. There is an increasing appreciation for the role of immune and metabolic dysfunction in the disease. ME/CFS has historically presented in outbreaks, often has a flu-like onset, and results in inflammatory symptoms. Patients suffer from severe fatigue and postexertional malaise. There is little known about the metabolism of specific immune cells in patients with ME/CFS. To investigate immune metabolism in ME/CFS, we isolated CD4+ and CD8+ T cells from 53 patients with ME/CFS and 45 healthy controls. We analyzed glycolysis and mitochondrial respiration in resting and activated T cells, along with markers related to cellular metabolism and plasma cytokines. We found that ME/CFS CD8+ T cells had reduced mitochondrial membrane potential compared with those from healthy controls. Both CD4+ and CD8+ T cells from patients with ME/CFS had reduced glycolysis at rest, whereas CD8+ T cells also had reduced glycolysis following activation.
Patients with ME/CFS had significant correlations between measures of T cell metabolism and plasma cytokine abundance that differed from correlations seen in healthy control subjects. Our data indicate that patients have impaired T cell metabolism consistent with ongoing immune alterations in ME/CFS that may illuminate the mechanism behind this disease
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https://dm5migu4zj3pb.cloudfront.net/manuscripts/132000/132185/JCI132185.v3.pdf

Andy · Oct 15, 2020

Mij said: ↑

https://dm5migu4zj3pb.cloudfront.net/manuscripts/132000/132185/JCI132185.v3.pdf
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That paper is discussed here, ME/CFS patients exhibit altered T cell metabolism and cytokine associations (2019) Mandarano, Hanson et al

Andy · Oct 20, 2020

@Simon M , did you see this one? Of any interest?

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Immunometabolic profiling of T cells from .. relapsing-remitting [MS] .. impairment in glycolysis and mitochondrial respiration, 2017, Matarese et al

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Immunometabolic profiling of T cells from .. relapsing-remitting [MS] .. impairment in glycolysis and mitochondrial respiration, 2017, Matarese et al

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