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Targeting pyruvate kinase M2 (PKM2) reduces T cell pathogenicity in multiple sclerosis.
Elena Ellmeier1, Alyssa Schnabl1, Julia Meissel1
1Division of Immunology, Otto Loewi Research Center, Medical University of Graz, Graz, Austria.
Ebiomedicine
|May 28, 2026
Summary
Pyruvate kinase M2 (PKM2) is elevated in T cells of multiple sclerosis (MS) patients. Targeting PKM2 reduces T cell inflammation, suggesting it as a potential therapeutic target for MS and autoimmune diseases.
Area of Science:
- Immunology
- Metabolic pathways
- Enzyme function
Background:
- Pyruvate kinase M2 (PKM2) exhibits moonlighting activities influencing T cell inflammation in a mouse model of multiple sclerosis (MS).
- Limited understanding exists regarding PKM2 expression in human T cell subsets and its therapeutic potential in MS patients.
Purpose of the Study:
- To investigate PKM2 expression in circulating T cells of healthy controls and MS patients.
- To analyze PKM2 isomerisation in peripheral blood mononuclear cells (PBMCs).
- To evaluate the impact of PKM2 targeting on T cell inflammatory profiles in MS.
Main Methods:
- Observational, case-control study design.
- Evaluation of PKM2 expression in human T cell subsets (naïve, effector, memory).
- Pharmacological targeting of PKM2 and assessment of cytokine production (IFN-γ, IL-5, IL-13, IL-17).
- Analysis of PKM2 monomer percentage in PBMCs.
Main Results:
- Higher PKM2 levels were observed in effector and memory T cells compared to naïve T cells.
- PKM2 expression correlated with age and disease duration in MS patients.
- Th17/Tc17 subsets showed the highest PKM2 expression.
- PKM2 inhibition preferentially reduced IFN-γ, IL-5, IL-13, and IL-17 production in MS T cells.
- MS patients exhibited a higher percentage of PKM2 monomer in PBMCs, indicating increased moonlighting activity.
Conclusions:
- PKM2 expression is altered in T cells of MS patients.
- Targeting PKM2 demonstrates potential for limiting T cell-driven inflammation in MS.
- PKM2 inhibition may offer a therapeutic strategy for MS and other autoimmune diseases.
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