Regulatory T cells: From Foxp3 to tolerance-inducing therapies.

Abstract

The immune system balances self-tolerance and threat defense; regulatory T cells (Tregs) enforce this equilibrium. This review follows their journey from the disputed suppressor T-cell era to the Foxp3-defined lineage and then integrates how Tregs recalibrate antigen-presenting cells and cytokine networks to sustain immune quiescence and restore homeostasis. These insights shape emerging therapies that expand endogenous Tregs in vivo with low-dose IL-2 or employ ex vivo-engineered cells to re-establish immune balance. We conclude by outlining key challenges-stability, tissue targeting, and scalability-for durable tolerance and therapeutic applications of recently clarified Treg-mediated tissue-specific homeostasis.