15 February 2007 | Yisong Y. Wan & Richard A. Flavell
Regulatory T cells (T(R)) are crucial for maintaining self-tolerance and immune homeostasis. Foxp3 is a key transcription factor that regulates T(R) development and function. Previous studies suggested that Foxp3 acts as a binary on/off switch for T(R) function, but recent evidence indicates that reduced Foxp3 expression can lead to immune disorders. This study shows that decreased Foxp3 expression in T(R) cells results in an aggressive autoimmune syndrome similar to scurfy mice, without affecting thymic development or Foxp3-expressing cell generation. T(R) cells with reduced Foxp3 expression lose their immunosuppressive function and become T-helper 2 (T(H2)) effector cells, contributing to immune diseases. These findings suggest that decreased Foxp3 expression subverts T(R) function and converts them into effector cells, which is important for understanding immune disorders. The study used a mouse model with reduced Foxp3 expression to investigate these effects, showing that T(R) cells with reduced Foxp3 expression lose their suppressive function and become T(H2) effector cells, leading to immune diseases. The study also found that T(R) cells with reduced Foxp3 expression can be converted into T(H2) effector cells even in a T(H1)-polarizing environment, contributing to immune diseases. These findings provide important insights into the regulation of T(R) function and the aetiology of immune disorders.Regulatory T cells (T(R)) are crucial for maintaining self-tolerance and immune homeostasis. Foxp3 is a key transcription factor that regulates T(R) development and function. Previous studies suggested that Foxp3 acts as a binary on/off switch for T(R) function, but recent evidence indicates that reduced Foxp3 expression can lead to immune disorders. This study shows that decreased Foxp3 expression in T(R) cells results in an aggressive autoimmune syndrome similar to scurfy mice, without affecting thymic development or Foxp3-expressing cell generation. T(R) cells with reduced Foxp3 expression lose their immunosuppressive function and become T-helper 2 (T(H2)) effector cells, contributing to immune diseases. These findings suggest that decreased Foxp3 expression subverts T(R) function and converts them into effector cells, which is important for understanding immune disorders. The study used a mouse model with reduced Foxp3 expression to investigate these effects, showing that T(R) cells with reduced Foxp3 expression lose their suppressive function and become T(H2) effector cells, leading to immune diseases. The study also found that T(R) cells with reduced Foxp3 expression can be converted into T(H2) effector cells even in a T(H1)-polarizing environment, contributing to immune diseases. These findings provide important insights into the regulation of T(R) function and the aetiology of immune disorders.