Recirculating regulatory T cells mediate thymic regeneration through amphiregulin following damage

Area of Science:

• Immunology
• Regenerative Medicine

Background:

• Thymic injury from disease or cancer treatment impairs T cell production, increasing infection and cancer vulnerability.
• Regulatory T (Treg) cells play a critical role in immune homeostasis and are implicated in tissue repair.

Purpose of the Study:

• To investigate the role of regulatory T (Treg) cells in thymic regeneration following acute injury.
• To identify mechanisms by which Treg cells promote thymic recovery and explore therapeutic potential.

Main Methods:

• Utilized various acute injury models in mice to study thymic regeneration.
• Employed Treg cell depletion and adoptive transfer experiments.
• Conducted parabiotic and adoptive transfer models to track Treg cell populations.
• Performed single-cell analyses to identify regenerative factors expressed by Treg cells.
• Investigated the function of amphiregulin in Treg cell-mediated regeneration.
• Identified analogous Treg cell populations in the human thymus.

Main Results:

• Treg cell frequencies increased in the thymus during acute injury.
• Depletion of Treg cells significantly impaired thymic regeneration, affecting both thymocytes and stromal cells.
• Adoptive transfer of Treg cells promoted thymic regeneration.
• Circulating Treg cells, not tissue-resident or recent thymic emigrants, expanded during injury.
• Single-cell analysis revealed that recirculating Treg cells express regenerative factors, including amphiregulin.
• Deletion of amphiregulin in Treg cells compromised regeneration in injured thymuses.
• A comparable CD39+ICOS+ Treg cell population was found in the human thymus.

Conclusions:

• Regulatory T (Treg) cells are essential for thymic regeneration after injury.
• The cytokine amphiregulin, expressed by circulating Treg cells, is a key mediator of thymic repair.
• Targeting Treg cells and their regenerative factors presents a promising therapeutic strategy for immunosuppression caused by aging or treatment.