The regulation of Foxp3 expression in regulatory CD4(+)CD25(+)T cells: Multiple pathways on the road

Regulatory T cells (Treg cells) have been well documented to have a crucial physiological role in preventing the development of autoimmune diseases and keeping self-tolerance. Foxp3, a recently identified member of the forkhead transcription factors, serves as a master regulator for the development and function of CD4(+)D25(+) Treg cells. Though it is well defined that Foxp3 expression is sufficient to program CD4(+)CD25(+) Treg cell development, the physiological factors initiating intracellular Foxp3 expression remain poorly understood so far. In the present manuscript, we try to summarize the recent advances regarding the regulatory roles of T-cell receptor (TCR), co-stimulatory molecules, interleukin-2 (IL-2), transforming growth factor-beta (TGF-beta) and beyond pathways on Foxp3 expression.