Deletion of STIM1 in Treg cells protects against lung fibrosis and associated cardiovascular complications in a pre-clinical mouse model - PubMed
4 hours ago
- #IPF
- #STIM1
- #Treg cells
- Idiopathic pulmonary fibrosis (IPF) is a progressive and incurable lung disease with excessive tissue remodeling and impaired gas exchange.
- Regulatory T-cells (Tregs) are diminished in IPF, contributing to inflammation and tissue damage.
- STIM1, a regulator of intracellular calcium, is upregulated in Treg cells from IPF patients and bleomycin-induced lung injury mice.
- Upregulation of STIM1 in Treg cells leads to increased apoptosis, reduced Foxp3 expression, and worsened pulmonary and cardiac fibrosis.
- Treg-specific STIM1 knockout mice (TregSTIM1-/-) show preserved Treg survival and function, reduced fibrosis, and improved endothelial function.
- TregSTIM1-/- mice maintain endothelial nitric oxide synthase (eNOS) phosphorylation and nitric oxide (NO) signaling, protecting redox balance.
- Improved NO bioavailability in TregSTIM1-/- mice correlates with reduced lung resistance, better compliance, and enhanced survival.
- STIM1 in Tregs links immune regulation, redox balance, and fibrosis, suggesting it as a therapeutic target for IPF.