Naturally arising regulatory T (
Treg) cells express the
transcription factor FoxP3, which critically controls the development and function of
Treg cells.
FoxP3 interacts with another
transcription factor Runx1 (also known as
AML1). Here, we showed that
Treg cell-specific deficiency of Cbfbeta, a cofactor for all Runx proteins, or that of Runx1, but not Runx3, induced lymphoproliferation,
autoimmune disease, and hyperproduction of
IgE. Cbfb-deleted
Treg cells exhibited
impaired suppressive function in vitro and in vivo, with altered
gene expression profiles including
attenuated expression of
FoxP3 and high expression of interleukin-4. The Runx complex bound to more than 3000 gene loci in
Treg cells, including the
Foxp3 regulatory regions and the Il4 silencer. In addition,
knockdown of
RUNX1 showed that
RUNX1 is required for the optimal regulation of
FoxP3 expression in human
T cells. Taken together, our results indicate that the Runx1-Cbfbeta heterodimer is indispensable for in vivo
Treg cell function, in particular, suppressive activity and optimal expression of
FoxP3.
