Mitochondrial functionality and metabolism in T cells from progressive multiple sclerosis patients

Abstract

Patients with primary progressive (PP) and secondary progressive (SP) forms of multiple sclerosis (MS) exhibit a sustained increase in the number of Th1, T cytotoxic type-1 and Th17 cells in peripheral blood, suggesting that the progressive phase is characterized by a permanent peripheral immune activation. As T cell functionality and activation are strictly connected to their metabolic profile, we investigated the mitochondrial functionality and metabolic changes of T cell subpopulations in a cohort of progressive MS patients. T cells from progressive patients were characterized by low proliferation and increase of terminally differentiated/exhausted cells. T cells from PP patients showed lower Oxygen Consumption Rate and Extracellular Acidification Rate, lower mitochondrial mass, membrane potential and respiration than those of SP patients, a downregulation of transcription factors supporting respiration and higher tendency to shift towards glycolysis upon stimulation. Furthermore, PP effector memory T cells were characterized by higherGlucose transporter -1 levels and a higher expression of glycolytic-supporting genes if compared to SP patients. Overall, our data suggest that profound differences exist in the phenotypic and metabolic features of T cells from PP and SP patients, even though the two clinical phenotypes are considered part of the same disease spectrum.Keywords: flow cytometry r metabolism r mitochondria r multiple sclerosis r T cells Additional supporting information may be found online in the Supporting Information section at the end of the article.

Marked T cell activation, senescence, exhaustion and skewing towards TH17 in patients with COVID-19 pneumonia

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Altered bioenergetics and mitochondrial dysfunction of monocytes in patients with COVID‐19 pneumonia

“…Table 2 reports mAbs clones, catalog numbers, type of fluorochrome used, and mAbs dilutions. Mitochondrial mass was analyzed by staining cells with MitoTracker green (MT Green, Thermo Fisher) (De Biasi et al , 2019). Mitochondrial membrane potential was analyzed by staining cells with 1,1ʹ,3,3ʹ‐tetraethyl‐5,5ʹ,6,6ʹ‐tetrachloroimidacarbocyanine iodide (JC‐1, Thermo Fisher) (Cossarizza et al , 2019).…”

Increased plasma levels of mitochondrial DNA and pro-inflammatory cytokines in patients with progressive multiple sclerosis

“…Patients were recruited at the MS Center of the Neurology Clinic of the University Hospital-NOCSAE in Modena during their planned routine visits, in the framework of a recently published clinical study De Biasi et al, 2019). All subjects gave written informed consent in agreement with the Declaration of Helsinki.…”