Reporter effects

The Foxp3^tm2Ayr (Foxp3^gfp) reporter mouse, which expresses enhanced green fluorescent protein (GFP) fused to the amino-terminal region of the transcription factor Foxp3, is widely used to track regulatory T cells (T_reg cells) in vivo. In Immunity, Bettini et al. and Darce et al. report that the chimeric Foxp3-GFP protein has altered functions relative to those of native Foxp3, with consequences for the differentiation, genomic signature and regulatory function of T_reg cells and the onset of autoimmunity in various mouse models. Darce et al. report less pathology in the K/BxN mouse model of arthritis, whereas Bettini et al. report considerably accelerated diabetes in Foxp3^gfp mice on the NOD (nonobese diabetic) background. Defective association of Foxp3-GFP with Eos, Tip60 and HDAC7, proteins known to bind to the amino terminus of Foxp3, may explain the T_reg cell insufficiency and enhanced diabetes of Foxp3^gfp NOD mice. The greater efficiency of Foxp3^gfp T_reg cells in blocking differentiation into the T_H17 subset of helper T cells may explain the amelioration of arthritis in Foxp3^gfp K/BxN mice. Thus, the molecular substrate of T_reg cell effector functions varies depending on the physiological context.

Immunity 36, 717–730 & 731–741 (2012)