Friend of GATA-1 represses GATA-3-dependent activity in CD4(+) T cells

The development of naive CD4(+) T cells into a T helper (Th) 2 subset capab le of producing interleukin (IL)-4, IL-5, and IL-13 involves a signal trans ducer and activator of transcription (Stat)6-dependent induction of GATA-3 expression, followed by Stat6-independent GATA-3 autoactivation. The friend of GATA (FOG)-1 protein regulates GATA transcription factor activity in se veral stages of hematopoietic development including erythrocyte and megakar yocyte differentiation, but whether FOG-1 regulates GATA-3 in T cells is un certain. We show that FOG-1 can repress GATA-3-dependent activation of the IL-5 promoter in T cells. Also, FOG-1 overexpression during primary activat ion of naive T cells inhibited Th2 development in CD4(+)-T cells. FOG-1 ful ly repressed GATA-3-dependent Th2 development and GATA-3 autoactivation, bu t not Stat6-dependent induction of GATA-3. FOG-1 overexpression repressed d evelopment of Th2 cells from naive T cells, but did not reverse the phenoty pe of fully committed Th2 cells. Thus, FOG-1 may be one factor capable of r egulating the Th2 development.