CD4+ Tregs Drive Post-Ischemic Sprouting Angiogenesis via Endothelial YY1/MAML1 Reactivation - PubMed
3 hours ago
- #Diabetes
- #Tregs
- #Angiogenesis
- CD4+ regulatory T-cells (Tregs) are reduced in type 2 diabetes after ischemic injury, impairing vascular regeneration.
- Endothelial cells upregulate transcription factor YY1 during post-ischemic regeneration, but this response is blunted in diabetic conditions.
- Endothelial-specific deletion of YY1 leads to defective vascular regeneration following ischemia.
- YY1 binds to the MAML1 promoter, activating its transcription by recruiting histone modifiers like SETD1A, MLL1, MLL2, WDR5, and p300.
- Tregs enhance vascular regeneration through paracrine signaling, even in type 2 diabetes mice.
- Adoptive Treg transfer restores regenerative capacity by reactivating the endothelial YY1/MAML1 axis.
- The Treg-YY1-MAML1 pathway is identified as a key regulator of endothelial function and vascular repair in diabetes-associated microvascular dysfunction.