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Updated: Oct 10, 2025
08:22
Isolation and Flow Cytometric Assessment of Neuroimmune Interactions in a Mini-Stroke Murine Model
Published on: June 20, 2025
175
RAGE-mediated T cell metabolic reprogramming shapes T cell inflammatory response after stroke
Yueman Zhang1, Fengshi Li2, Chen Chen1
1Department of Anesthesiology, State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Summary
Post-stroke, the receptor for advanced glycation end products (RAGE) triggers CD4+ T cell metabolic changes. Neutralizing RAGE with soluble RAGE (sRAGE) improves recovery by restoring T cell balance and reducing inflammation.
Area of Science:
- Immunology
- Neuroscience
- Metabolic Research
Background:
- Stroke induces metabolic reprogramming in CD4+ T cells, leading to imbalanced T cell differentiation.
- The precise mechanisms regulating this post-stroke metabolic shift remain unclear.
- CD4+ T cell dysfunction is a potential target for immunotherapy after stroke.
Purpose of the Study:
- To elucidate the regulatory mechanism of CD4+ T cell metabolic reprogramming post-stroke.
- To investigate the role of the receptor for advanced glycation end products (RAGE) in this process.
- To evaluate the therapeutic potential of targeting RAGE for stroke recovery.
Main Methods:
- Combined transcription and metabolomics analyses.
- Flow cytometry and conditional knockout mice models.
- Administration of soluble RAGE (sRAGE) post-stroke.
Main Results:
- RAGE mediates ischemic signals to CD4+ T cells, inducing acetyl-CoA carboxylase 1 (ACC1)-dependent metabolic reprogramming.
- sRAGE treatment reversed enhanced fatty acid synthesis in CD4+ T cells and corrected Treg/Th17 imbalance.
- Post-stroke sRAGE administration reduced infarct volume and improved functional recovery.
Conclusions:
- sRAGE acts as an immunometabolic modulator, improving ischemic stroke recovery.
- Inhibition of fatty acid synthesis by sRAGE promotes Treg polarization after cerebral ischemia.
- Targeting RAGE offers a novel therapeutic strategy for neuroinflammation following ischemic stroke.
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