Regulatory T (Treg) cells play a crucial role in maintaining peripheral tolerance, preventing autoimmune diseases, and limiting chronic inflammatory responses. However, they can also suppress beneficial immune responses, such as sterilizing immunity and anti-tumor immunity. The mechanisms of Treg cell action are multifaceted and include the production of inhibitory cytokines (e.g., IL-10 and TGFβ), cytolysis, metabolic disruption, and modulation of dendritic cell (DC) maturation or function. The transcription factor forkhead box P3 (FOXP3) is essential for Treg cell development and function, but its role in human Treg cells is less straightforward compared to murine models. Recent studies have identified additional inhibitory cytokines, such as IL-35, and mechanisms like adenosine production and cAMP transfer, which contribute to Treg cell suppression. The precise mechanisms and their relative importance in different disease contexts remain areas of active research. Additionally, there is growing evidence that effector T cells may not be passive recipients but can potently enhance Treg cell function through receptor-ligand interactions. Understanding these mechanisms is crucial for developing therapeutic strategies to manipulate Treg cells in the context of autoimmune diseases and cancer.Regulatory T (Treg) cells play a crucial role in maintaining peripheral tolerance, preventing autoimmune diseases, and limiting chronic inflammatory responses. However, they can also suppress beneficial immune responses, such as sterilizing immunity and anti-tumor immunity. The mechanisms of Treg cell action are multifaceted and include the production of inhibitory cytokines (e.g., IL-10 and TGFβ), cytolysis, metabolic disruption, and modulation of dendritic cell (DC) maturation or function. The transcription factor forkhead box P3 (FOXP3) is essential for Treg cell development and function, but its role in human Treg cells is less straightforward compared to murine models. Recent studies have identified additional inhibitory cytokines, such as IL-35, and mechanisms like adenosine production and cAMP transfer, which contribute to Treg cell suppression. The precise mechanisms and their relative importance in different disease contexts remain areas of active research. Additionally, there is growing evidence that effector T cells may not be passive recipients but can potently enhance Treg cell function through receptor-ligand interactions. Understanding these mechanisms is crucial for developing therapeutic strategies to manipulate Treg cells in the context of autoimmune diseases and cancer.