Regulatory T cells (T(regs)) have potential applications in clinical disease therapy， such as autoimmune diseases and transplant rejection. However， their numbers are limited. Forkhead box protein 3 (FoxP3) is a key transcription factor that controls T(reg) development and function. Here， we generated a cell-permeable fusion protein， protein transduction domain (PTD)-conjugated mouse FoxP3 protein (PTD-mFoxP3)， and evaluated whether PTD-mFoxp3 can alleviate rheumatoid arthritis (RA) in the collagen-induced arthritis (CIA) mouse model. As expected， PTD-mFoxP3 was transduced into cells effectively， and inhibited T cell activation and attenuated the cell proliferation. It decreased interleukin (IL) 2... More
Regulatory T cells (T(regs)) have potential applications in clinical disease therapy， such as autoimmune diseases and transplant rejection. However， their numbers are limited. Forkhead box protein 3 (FoxP3) is a key transcription factor that controls T(reg) development and function. Here， we generated a cell-permeable fusion protein， protein transduction domain (PTD)-conjugated mouse FoxP3 protein (PTD-mFoxP3)， and evaluated whether PTD-mFoxp3 can alleviate rheumatoid arthritis (RA) in the collagen-induced arthritis (CIA) mouse model. As expected， PTD-mFoxP3 was transduced into cells effectively， and inhibited T cell activation and attenuated the cell proliferation. It decreased interleukin (IL) 2 and interferon (IFN)-γ expression， and increased IL-10 expression in activated CD4(+)CD25(-) T cells. PTD-mFoxP3-transduced CD4(+)CD25(-) T cells attenuated proliferation of activated CD4(+)CD25(-) T cells. In addition， PTD-mFoxP3 blocked the Th17 differentiation programme in vitro and down-regulated IL-17 production from T cells by modulating induction and levels of retinoid-related orphan receptor gamma t (RORγt). Intra-articular delivery of PTD-mFoxP3 delayed disease incidence remarkably and alleviated autoimmune symptoms of CIA mice. Moreover， protective effects of PTD-mFoxP3 were associated with regulating the balance of T helper type 17 (Th17) and T(regs). These results suggest that PTD-mFoxP3 may be a candidate for RA therapy.
