Therapeutic Potential of Regulatory T Cells for Stem Cell Regulation: Insights from Treg-Mediated Enhancement of Limbal Stem Cell Functions

Regulatory T cells (Tregs) play a key role in immunomodulation and tissue regeneration. Limbal stem cells (LSCs) maintain corneal epithelial homeostasis, and limbal stem cell deficiency (LSCD) leads to visual impairment. Current LSCD treatments face donor shortages and graft rejection risks. The present study explored Tregs' therapeutic potential for LSCD in a mouse model of graded LSCD, and further explore the direct effect of Tregs on LSCs function by in vitro coculturing human-derived cells. Subconjunctival Tregs injection effectively treated mild and moderate LSCD in mouse models. Coculturing human LSCs with human Tregs promotes LSCs migration, proliferation, and stemness maintenance. Furthermore, amphiregulin (AREG), secreted by Tregs, was crucial to their therapeutic effects, as AREG-/- Tregs resulted in diminished efficacy on LSCD mice compared to wild-type Tregs. These findings highlighted Tregs as a promising treatment for LSCD, enhancing LSC function partially via AREG production. Overall design: Comparative gene expression profiling analysis of RNA-seq data for human limbal stem cells