Mitochondrial functionality and metabolism in T cells from progressive multiple sclerosis patients
| Autor: | Marcello Pinti, Domenico Lo Tartaro, Patrizia Sola, Lara Gibellini, Anna Maria Simone, Diana Ferraro, Milena Nasi, Simone Patergnani, Elena Bianchini, Sara De Biasi, Simone Pecorini, Gianluca Carnevale, Paolo Pinton, Francesca Vitetta, Andrea Cossarizza |
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| Rok vydání: | 2019 |
| Předmět: |
Adult
0301 basic medicine medicine.medical_specialty Multiple Sclerosis T-Lymphocytes T cell Immunology T cells Mitochondrion Biology NO 03 medical and health sciences Oxygen Consumption 0302 clinical medicine Downregulation and upregulation Internal medicine Respiration medicine Humans Immunology and Allergy Cytotoxic T cell Glycolysis Aged flow cytometry metabolism mitochondria multiple sclerosis Glucose Transporter Type 1 Multiple sclerosis Glucose transporter Middle Aged medicine.disease Mitochondria 030104 developmental biology Endocrinology medicine.anatomical_structure Female Immunologic Memory 030215 immunology |
| Zdroj: | European Journal of Immunology. 49:2204-2221 |
| ISSN: | 1521-4141 0014-2980 |
| Popis: | 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 higher Glucose 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. |
| Databáze: | OpenAIRE |
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