T cells display mitochondria hyperpolarization in human type 1 diabetes

• Published in: Scientific reports Vol. 7; no. 1; pp. 10835 - 11
• Main Authors: Chen, Jing, Chernatynskaya, Anna V., Li, Jian-Wei, Kimbrell, Matthew R., Cassidy, Richard J., Perry, Daniel J., Muir, Andrew B., Atkinson, Mark A., Brusko, Todd M., Mathews, Clayton E.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 07.09.2017; Nature Publishing Group
• Subjects: 631/250/38; 692/699/2743; Adenosine Triphosphate - metabolism; Apoptosis; Apoptosis - immunology; Bioenergetics; Biomarkers; Carbocyanines - administration & dosage; Cell activation; Cell proliferation; Diabetes; Diabetes mellitus; Diabetes Mellitus, Type 1 - immunology; Diabetes Mellitus, Type 1 - metabolism; Glycolysis; Humanities and Social Sciences; Humans; Hyperpolarization; Immunophenotyping; Lymphocyte Activation - genetics; Lymphocyte Activation - immunology; Lymphocytes; Lymphocytes T; Membrane Potential, Mitochondrial; Microscopy, Confocal; Mitochondria; Mitochondria - metabolism; multidisciplinary; Science; Science (multidisciplinary); T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; γ-Interferon
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-11056-9

T lymphocytes constitute a major effector cell population in autoimmune type 1 diabetes. Despite essential functions of mitochondria in regulating activation, proliferation, and apoptosis of T cells, little is known regarding T cell metabolism in the progression of human type 1 diabetes. In this study, we report, using two independent cohorts, that T cells from patients with type 1 diabetes exhibited mitochondrial inner-membrane hyperpolarization (MHP). Increased MHP was a general phenotype observed in T cell subsets irrespective of prior antigen exposure, and was not correlated with HbA1C levels, subject age, or duration of diabetes. Elevated T cell MHP was not detected in subjects with type 2 diabetes. T cell MHP was associated with increased activation-induced IFNγ production, and activation-induced IFNγ was linked to mitochondria-specific ROS production. T cells from subjects with type 1 diabetes also exhibited lower intracellular ATP levels. In conclusion, intrinsic mitochondrial dysfunction observed in type 1 diabetes alters mitochondrial ATP and IFNγ production; the latter is correlated with ROS generation. These changes impact T cell bioenergetics and function.