Abstract TP066: IL-2Rα Regulates Thalamo-Cortical Axons Plasticity Through JAK-STAT5a-Tcf712 Pathway Following Ischemic Stroke

Background: Disruption of axonal connections between thalamus and cortex leads to thalamic degeneration in cortical projection area after ischemic stroke. Recent studies have indicated that inflammatory factors, such as interleukin(IL), play a crucial role in modulating inter-regional neural transmission and critically drive the progression of neurological disorders. The binding of IL-2 to the interleukin-2 receptor subunit alpha (IL2Rα) activates the JAK-STAT5a signaling pathway, which is essential for maintaining immune homeostasis. However, it is unknown whether this pathway participates in axons plasticity between thalamus and cortex after stroke. Methods: Adult male C57BL/6 and IL2Rα knockout (KO) mice subjected to 45 min of middle cerebral artery occlusion (MCAO), followed by 3 through 28 days reperfusion. Thalamo-cortical functional connectivity were assessed by functional magnetic resonance imaging(fMRI). Long-term functional outcomes were determined by beam balance tests, adhesive tape touch and adhesive tape removal tests. RNA-seq identified differential gene expression and conducted functional enrichment analysis. Protein quantities of JAK-STAT5a pathway, transcription factors(Tcf712, Gbx2 and Lhx9), roundabout guidance receptor 1 (Robo1), IL2 and IL2Rα were assessed by western blot. Results: IL2Rα KO showed a significant increase in functional connectivity between the thalamus and several areas of the primary sensory cortex following cerebral ischemia compared to the wild-type mice following cerebral ischemia. Additionally, IL2Rα KO significantly improved functional outcomes at day 7 and 28. RNA-seq analysis revealed a marked decrease in the expression of Tcf712, Gbx2, and Lhx9. Moreover, protein levels of JAK, STAT5a, Tcf712, Gbx2, Lhx9, Robo1, IL2, and IL2Rα were significantly reduced, while STAT5a phosphorylation was notably increased after IL2Rα KO. Conclusion: Our findings suggest that IL2Rα may be a novel potential target of regulating thalamo-cortical axons plasticity, and clarifying the potential mechanism can provide a new idea for the regulation of IL-2Rα after cerebral ischemia.