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

TLDR

TGF‑β1 is a key immunosuppressive cytokine whose deficiency causes lethal autoimmunity, yet its precise mechanisms remain incompletely understood. The study investigates whether TGF‑β1 is required for maintenance of Foxp3 expression, regulatory function, and homeostasis in peripheral CD4⁺CD25⁺ regulatory T cells, but not for their thymic development. In TGF‑β1–deficient mice, peripheral T reg cells are reduced, Foxp3 expression and suppressor activity are decreased, establishing an essential link between TGF‑β1 signaling and peripheral T reg cell maintenance.

Abstract

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.