Metabolic Control of Autoimmunity and Tissue Inflammation in Rheumatoid Arthritis Original paper
Researched by:
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Divine Aleru
ID
Divine Aleru
Read MoreI am a biochemist with a deep curiosity for the human microbiome and how it shapes human health, and I enjoy making microbiome science more accessible through research and writing. With 2 years experience in microbiome research, I have curated microbiome studies, analyzed microbial signatures, and now focus on interventions as a Microbiome Signatures and Interventions Research Coordinator.
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Divine Aleru
Read More
Researched by:
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Divine Aleru
ID
Divine Aleru
Read More
Microbiome Signatures identifies and validates condition-specific microbiome shifts and interventions to accelerate clinical translation. Our multidisciplinary team supports clinicians, researchers, and innovators in turning microbiome science into actionable medicine.
Divine Aleru
What was studied?
The study focused on the role of metabolic reprogramming in rheumatoid arthritis (RA), specifically in how altered immune cell metabolism contributes to inflammation and tissue damage in the disease. It explored how metabolic pathways, such as glycolysis and lipid metabolism, influence the behavior of T cells, macrophages, and other immune cells in the rheumatoid joint. The research also delved into how mitochondrial dysfunction, oxidative stress, and the shift from oxidative phosphorylation (OxPhos) to glycolysis contribute to the pathophysiology of RA.
Who was studied?
The study primarily focused on rheumatoid arthritis (RA) patients, particularly their immune cells, such as CD4+ T cells, fibroblast-like synoviocytes (FLS), and macrophages. These immune cells were studied in the context of their altered metabolic functions and how these changes exacerbate the disease’s inflammatory process. The analysis involved understanding the metabolic alterations that occur within these cells, such as increased glycolysis, disrupted mitochondrial function, and changes in lipid metabolism, which contribute to RA’s chronic inflammation.
What were the most important findings?
The study found that RA immune cells exhibit significant metabolic reprogramming, which supports their activation and inflammatory behavior. Specifically, T cells in RA were shown to have altered glucose metabolism, primarily shunting glucose into the pentose phosphate pathway rather than being used for energy production via oxidative phosphorylation. This metabolic shift, along with mitochondrial dysfunction and oxidative stress, promotes tissue inflammation. Additionally, the study identified that synovial fibroblasts (FLS) rely on glutamine rather than glucose for their proliferation, suggesting that targeting glutamine metabolism could offer new therapeutic strategies for RA. The role of metabolic intermediates, such as lactate and succinate, was also highlighted as being critical for sustaining inflammation in the rheumatoid joint.
What are the greatest implications of this study?
The greatest implication of this study is that metabolic reprogramming in immune cells can serve as both a biomarker and a therapeutic target for rheumatoid arthritis. By understanding how the metabolic shifts in RA cells contribute to chronic inflammation, new treatments could be developed to target these metabolic pathways. For example, manipulating the glucose and glutamine metabolism of immune cells could help to restore immune homeostasis and potentially prevent the tissue destruction associated with RA. This metabolic approach could lead to more effective treatments with fewer side effects than current therapies, which primarily focus on immune suppression.