# Therapeutic potential of regulatory T cells for stem cell regulation: Insights from Treg-mediated enhancement of limbal stem cell functions

## TL;DR

Regulatory T cells (Tregs) can help treat corneal stem cell deficiency in mice by boosting stem cell function and reducing rejection risks.

## Contribution

This study demonstrates Tregs' therapeutic potential for limbal stem cell deficiency via amphiregulin-mediated enhancement.

## Key findings

- Subconjunctival Treg injection effectively treats mild and moderate limbal stem cell deficiency in mice.
- Tregs enhance human limbal stem cell migration, proliferation, and stemness in vitro.
- Amphiregulin is essential for Tregs' therapeutic effects on limbal stem cell deficiency.

## Abstract

Regulatory T cells (Tregs) play a key role in immunomodulation and tissue regeneration. Limbal stem cells (LSCs) maintain corneal epithelial homeostasis, and LSC 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 explored 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 promoted 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 highlight Tregs as a promising treatment for LSCD, enhancing LSC function partially via AREG production.

•Tregs injection effectively treats mild and moderate LSCD in mice•Tregs enhance LSC migration, proliferation, and stemness in vitro•Amphiregulin is crucial for Tregs’ therapeutic effects on LSCD

Tregs injection effectively treats mild and moderate LSCD in mice

Tregs enhance LSC migration, proliferation, and stemness in vitro

Amphiregulin is crucial for Tregs’ therapeutic effects on LSCD

Therapeutics; Immunology; Stem cells research