Poly(ADP-ribosyl)ation of FOXP3 Mediated by PARP-1 Regulates the Function of Regulatory T Cells [Cell Biology]

October 1st, 2015 by Luo, X., Nie, J., Wang, S., Chen, Z., Chen, W., Li, D., Hu, H., Li, B.

Poly(ADP-ribose) polymerase-1 (PARP-1) is an ADP-ribosylating enzyme participating in diverse cellular functions. The roles of PARP-1 in the immune system, however, have not been well understood. Here we find that PARP-1 interacts with FOXP3 and induces its poly(ADP-ribosyl)ation. By using PARP-1 inhibitors, we show that reduced poly(ADP-ribosyl)ation of FOXP3 results in not only FOXP3 stabilization and increased FOXP3 downstream genes, but also enhanced suppressive function of regulatory T cells (Treg). Our results suggest that PARP-1 negatively regulates the suppressive function of Treg cells at the post-translational level via FOXP3 poly(ADP-ribosyl)ation. This finding has implications in developing PARP-1 inhibitors as potential agents for the prevention and treatment of autoimmune diseases.