TGF-β1 maintains suppressor function and Foxp3 expression in CD4+CD25+ regulatory T cells

JC Marie, JJ Letterio, M Gavin… - The Journal of …, 2005 - rupress.org
The Journal of experimental medicine, 2005rupress.org
Transforming growth factor (TGF)-β1 is a major pluripotential cytokine with a pronounced
immunosuppressive effect and its deficiency results in lethal autoimmunity in mice. However,
mechanisms of its immunosuppressive action are not completely understood. Here, we
report that TGF-β1 supports the maintenance of Foxp3 expression, regulatory function, and
homeostasis in peripheral CD4+ CD25+ regulatory T (T reg) cells, but is not required for
their thymic development. We found that in 8–10-d-old TGF-β1–deficient mice, peripheral …
Transforming growth factor (TGF)-β1 is a major pluripotential cytokine with a pronounced immunosuppressive effect and its deficiency results in lethal autoimmunity in mice. However, mechanisms of its immunosuppressive action are not completely understood. Here, we report that TGF-β1 supports the maintenance of Foxp3 expression, regulatory function, and homeostasis in peripheral CD4+CD25+ regulatory T (T reg) cells, but is not required for their thymic development. We found that in 8–10-d-old TGF-β1–deficient mice, peripheral, but not thymic, T reg cells are significantly reduced in numbers. Moreover, our experiments suggest that a defect in TGF-β–mediated signaling in T reg cells is associated with a decrease in Foxp3 expression and suppressor activity. Thus, our results establish an essential link between TGF-β1 signaling in peripheral T reg cells and T reg cell maintenance in vivo.
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