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Isolation and Flow Cytometric Assessment of Neuroimmune Interactions in a Mini-Stroke Murine Model
Published on: June 20, 2025
Involvement of Mincle and Syk in the changes to innate immunity after ischemic stroke
Yukiya Suzuki1, Yusuke Nakano, Keisuke Mishiro
11] Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu 501-1196, Japan [2] Laboratory of Drug Informatics, Gifu Pharmaceutical University, Gifu, 501-1196, Japan.
Abstract:
Accumulating evidence shows that post-ischemic inflammation originated by Toll-like receptors (TLR) plays critical roles in ischemic stroke. However, the functions of other innate immune receptors are poorly understood in cerebral ischemia. Macrophage-inducible C-type lectin, Mincle, is one of the innate immune receptor C-type lectin-like receptor (CLR) to response against dying cells. In the present study, we showed that Mincle, its ligand SAP130, and its downstream phospho-Syk/Syk were upregulated after ischemia, and that Mincle is expressed in immune and non-immune cells in the ischemic brains of mice and human. We treated mice with piceatannol, a Syk inhibitor, and consequently the infarct volume and swelling were suppressed by piceatannol. The levels of phospho-Syk, MMP9 and ICAM-1 were downregulated, and the level of Claudin5 was uplegurated in piceatannol-treated groups. These data indicate that innate immune system, such as Mincle and Syk plays a pivotal role in the pathogenesis after the ischemia and reperfusion.
Insights
Post-ischemic inflammation involves Mincle, a C-type lectin-like receptor, and Syk signaling in ischemic stroke. Inhibiting Syk with piceatannol reduced stroke damage, highlighting Mincle-Syk as a therapeutic target.
Area of Science:
- Immunology
- Neuroscience
- Pathology
Background:
- Post-ischemic inflammation is crucial in ischemic stroke, with Toll-like receptors (TLRs) implicated.
- The role of other innate immune receptors, like Mincle (Macrophage-inducible C-type lectin), in cerebral ischemia remains unclear.
Purpose of the Study:
- To investigate the role of Mincle and its signaling pathway in the pathogenesis of ischemic stroke.
- To evaluate the therapeutic potential of inhibiting the Mincle-Syk pathway.
Main Methods:
- Upregulation of Mincle, SAP130, and phospho-Syk/Syk was assessed post-ischemia in mice and human brain samples.
- Mice were treated with piceatannol, a Syk inhibitor, to evaluate its effects on infarct volume, swelling, and molecular markers.
- Levels of phospho-Syk, MMP9, ICAM-1, and Claudin5 were analyzed in treated and control groups.
Main Results:
- Mincle, SAP130, and phospho-Syk/Syk were upregulated following ischemia.
- Mincle expression was observed in both immune and non-immune cells in ischemic brain tissue.
- Piceatannol treatment significantly reduced infarct volume and brain swelling.
- Downregulation of phospho-Syk, MMP9, and ICAM-1, and upregulation of Claudin5 were observed in the piceatannol-treated group.
Conclusions:
- The Mincle-Syk signaling pathway is activated in ischemic stroke and contributes to pathogenesis.
- Inhibition of Syk offers a potential therapeutic strategy for mitigating ischemic stroke injury.
- These findings underscore the critical role of the innate immune system in post-ischemia reperfusion injury.
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