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International journal of molecular sciences2024; 25(21); doi: 10.3390/ijms252111513

Enhanced ROS Production and Mitochondrial Metabolic Shifts in CD4+ T Cells of an Autoimmune Uveitis Model.

Abstract: Equine recurrent uveitis (ERU) is a spontaneously occurring autoimmune disease and one of the leading causes of blindness in horses worldwide. Its similarities to autoimmune-mediated uveitis in humans make it a unique spontaneous animal model for this disease. Although many aspects of ERU pathogenesis have been elucidated, it remains not fully understood and requires further research. CD4+ T cells have been a particular focus of research. In a previous study, we showed metabolic alterations in CD4+ T cells from ERU cases, including an increased basal oxygen consumption rate (OCR) and elevated compensatory glycolysis. To further investigate the underlying reasons for and consequences of these metabolic changes, we quantified reactive oxygen species (ROS) production in CD4+ T cells from ERU cases and compared it to healthy controls, revealing significantly higher ROS production in ERU-affected horses. Additionally, we aimed to define mitochondrial fuel oxidation of glucose, glutamine, and long-chain fatty acids (LCFAs) and identified significant differences between CD4+ T cells from ERU cases and controls. CD4+ T cells from ERU cases showed a lower dependency on mitochondrial glucose oxidation and greater metabolic flexibility for the mitochondrial oxidation of glucose and LCFAs, indicating an enhanced ability to switch to alternative fuels when necessary.
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Publication Date: 2024-10-26 PubMed ID: 39519064PubMed Central: PMC11545935DOI: 10.3390/ijms252111513Google Scholar: Lookup
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  • Journal Article

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This study explores the elevated occurrence of an inflammatory eye disease called equine recurrent uveitis (ERU) in horses, with a particular focus on the metabolic alterations in CD4+ T cells, a type of immune cell. The researchers found higher production of reactive oxygen species (ROS) in diseased horses, as well as significant changes in their cells’ use of different metabolic fuels, suggesting that these changes may play a part in ERU occurrence.

Study Context

  • The research is aimed at understanding the pathogenesis of equine recurrent uveitis (ERU), an autoimmune disease in horses that often leads to blindness.
  • ERU shares similarities with human autoimmune-mediated uveitis, hence why the discoveries made in this type of research can potentially aid in the understanding and treatment of the human condition.
  • Despite previous research, the pathogenesis of ERU is not yet completely understood, and this study contributes to that ongoing investigation.

Role of CD4 T Cells in ERU

  • The authors have previously identified metabolic changes in the CD4 T cells of horses with ERU, including increased basal oxygen consumption rate (OCR), and raised compensatory glycolysis.
  • CD4 T cells are vital in the immune response, hence understanding their role and behavior is crucial when investigating an autoimmune disease like ERU.

Increased ROS Production

  • In this paper, it is reported that CD4 T cells from ERU-affected horses produce a significantly higher amount of reactive oxygen species (ROS) when compared to healthy controls.
  • ROS are chemically reactive molecules that play roles in cell signaling and homeostasis. High levels can be damaging, and this may be linked to the disease progression.

Mitochondrial Metabolic Shifts

  • Investigating the mitochondrial fuel oxidation of glucose, glutamine, and long-chain fatty acids (LCFAs), the study reports significant differences in the CD4 T cells of ERU-affected and healthy horses.
  • CD4 T cells from ERU cases showed less reliance on mitochondrial glucose oxidation and higher metabolic versatility when oxidizing glucose and LCFAs.
  • This greater ability to switch to alternative fuels when needed (metabolic flexibility) could be a response to physiological changes brought about by the disease or a contributing factor to its onset.

Cite This Article

APA
Söth R, Hoffmann ALC, Deeg CA. (2024). Enhanced ROS Production and Mitochondrial Metabolic Shifts in CD4+ T Cells of an Autoimmune Uveitis Model. Int J Mol Sci, 25(21). https://doi.org/10.3390/ijms252111513

Publication

International journal of molecular sciences
ISSN: 1422-0067
NlmUniqueID: 101092791
Country: Switzerland
Language: English
Volume: 25
Issue: 21

Researcher Affiliations

Söth, Ronja
  • Chair of Physiology, Department of Veterinary Sciences, Ludwig Maximilian University of Munich, D-82152 Martinsried, Germany.
Hoffmann, Anne L C
  • Chair of Physiology, Department of Veterinary Sciences, Ludwig Maximilian University of Munich, D-82152 Martinsried, Germany.
Deeg, Cornelia A
  • Chair of Physiology, Department of Veterinary Sciences, Ludwig Maximilian University of Munich, D-82152 Martinsried, Germany.

MeSH Terms

  • Animals
  • Reactive Oxygen Species / metabolism
  • Uveitis / metabolism
  • Uveitis / veterinary
  • Uveitis / immunology
  • Uveitis / pathology
  • CD4-Positive T-Lymphocytes / metabolism
  • CD4-Positive T-Lymphocytes / immunology
  • Horses
  • Mitochondria / metabolism
  • Autoimmune Diseases / metabolism
  • Autoimmune Diseases / immunology
  • Disease Models, Animal
  • Glucose / metabolism
  • Horse Diseases / metabolism
  • Horse Diseases / immunology
  • Glycolysis
  • Oxygen Consumption
  • Fatty Acids / metabolism
  • Oxidation-Reduction

Grant Funding

  • DFG DE 719/4-4 / Deutsche Forschungsgemeinschaft

Conflict of Interest Statement

The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

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