T Cells Display Mitochondria Hyperpolarization in Human Type 1 Diabetes

Overview

Journal Sci Rep

Specialty Science

Date 2017 Sep 9

PMID 28883439

Citations 25

Authors

Jing Chen

Anna V Chernatynskaya

Jian-Wei Li

Matthew R Kimbrell

Richard J Cassidy

Daniel J Perry

Andrew B Muir

Mark A Atkinson

Todd M Brusko

Clayton E Mathews

Affiliations

Soon will be listed here.

Abstract

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.

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