T Cell Mitochondrial Dysfunction Linked to Human Type 1 Diabetes

Share this content:
Previous studies in animal models of type 1 diabetes suggest that mitochondrial dysfunction in the T cell compartment contribute to autoimmunity.
Previous studies in animal models of type 1 diabetes suggest that mitochondrial dysfunction in the T cell compartment contribute to autoimmunity.

NEW ORLEANS — New research suggests that T cell mitochondrial dysfunction in patients with type 1 diabetes is intrinsic to T cells and leads to abnormal T cell regulation.

“T cell function is closely regulated by cellular energy metabolism,” said Jing Chen, PhD, of the University of Florida, Gainesville. “Abnormal mitochondrial dysfunction in T cells results in immune dysregulation and development of autoimmunity.  These changes eventually participate in the pathogenesis of human type 1 diabetes.”

Dr Chen and fellow researchers presented the results at the American Diabetes Association (ADA) Scientific Sessions.

 

In an interview with Endocrinology Advisor, Dr Chen explained that T cell mitochondrial dysfunction has been associated with some human autoimmune diseases. 

“Studies using animal models of type 1 diabetes also suggest that mitochondrial dysfunction in the T cell compartment contribute to autoimmunity,” she said. “Yet, T cell mitochondrial function has not been investigated in human type 1 diabetes.”

In the study, Dr Chen and colleagues identified T cell mitochondrial inner membrane hyperpolarization (MHP) in patients with type 1 diabetes (P=.027; n=29) and compared them with healthy controls (n=38).

Researchers found that T cell MHP was not associated with age, disease duration, or hemoglobin A1c levels.

In a second cohort, consisting of 39 patients with type 1 diabetes and 28 controls, presence of T cell MHP in type 1 diabetes was verified (P=.0042).

Functional analysis demonstrated that T cell MHP yielded altered activation-induced interferon production (P=.022), which was further associated with generation of activation-induced mitochondrial reactive oxygen species (mtROS; R2=0.097; P=.023).

Furthermore, T cells from patients with type 1 diabetes displayed lower cellular adenosine triphosphate (ATP) content at rest (64.79 ± 8.706 vs 97.64 ± 12.33 pmol/mg protein; P=.046), while in vitro activation raised the ATP level in T cells from type 1 diabetes.

Among individuals who were positive for multiple autoantibodies, T cells were resistant to activation-induced apoptosis (AICD).

In other data, CD8+ T cells from an individual with T cell MHP demonstrated higher antigen specific cytotoxicity when compared with those from normal mitochondrial membrane potential.

Dr Chen and colleagues also found that the expression of genes associated with mitochondrial function—such as those regulating membrane potential, fission and fusion, apoptosis, translocation and transport—failed to upregulate in T cells from patients with type 1 diabetes after in vitro activation compared with healthy controls.

Additionally, genetic analysis revealed associations between risk alleles of type 1 diabetes and T cell mitochondrial dysfunction, including MHP, mtROS, and AICD.

“Genetic predispositions determined intrinsic mitochondria dysfunction in T cells from patients with type 1 diabetes,” Dr Chen concluded. “CD4 and CD8 T cells with mitochondrial hyperpolarization display functional changes.”

Disclosure: Dr Chen reports no relevant financial disclosures.


Reference

  1. Chen J, Chernatynskaya AV, Kimbrell MR, et al. Abstract 375-OR/375. T Cell Mitochondrial Dysfunction in Human Type 1 Diabetes. Presented at: ADA 76th Scientific Sessions; June 10-14, 2016; New Orleans.
You must be a registered member of Endocrinology Advisor to post a comment.

Upcoming Meetings

Sign Up for Free e-Newsletters