Targeting T Cell Metabolism and Polarization to Modulate Post-Stroke Immune Responses

BackgroundT cells drive post-stroke secondary brain injury, with the Th17/Treg balance shaping post-stroke inflammation. Soraphen A (SorA) inhibits Th17 polarization while preserving Tregs.

We examined SorA’s effects on post-stroke T cell activation – distinguishing antigen-specific from bystander activation – including inflammatory conditions induced by LPS.MethodsMale Nur77GFP mice (12–14 weeks) underwent tMCAO. At reperfusion, mice received intraperitoneal LPS or vehicle; SorA or vehicle was given 2 h later and daily thereafter.

MRI at 16 h and 7 d confirmed infarcts and measured lesion volumes. Functional outcomes were assessed by daily scoring and behavioral tests before surgery and at 2 and 6 d.

T cell activation and polarization were analyzed by flow cytometry in brain, lungs, spleen, blood, and lymph nodes at 16 h, 2, 3, and 7 d, with GFP indicating antigen-specific activation.ResultsLPS worsened functional outcomes and increased peripheral T cell activation post-stroke. SorA improved functional recovery, reduced peripheral T cell activation and enhanced antigen-specific T cell activation.