Cell penetrable mouse forkhead box P3 suppresses type 1 T helper cell-mediated immunity in a murine model of delayed-type hypersensitivity

Abstract

Forkhead box P3 (FOXP3), which is a transcription factor, has a primary role in the development and function of regulatory T cells, and thus contributes to homeostasis of the immune system. A previous study generated a cell permeable fusion protein of mouse FOXP3 conjugated to a protein transduction domain (PTD mFOXP3) that successfully blocked differentiation of type 17 T helper cells in vitro and alleviated experimental arthritis in mice. In the present study, the role of PTD mFOXP3 in type 1 T helper (Th1) cell mediated immunity was investigated and the possible mechanisms for its effects were explored. Under Th1 polarization conditions, cluster of differentiation 4+ T cells were treated with PTD mFOXP3 and analyzed by flow cytometry in vitro, which revealed that PTD mFOXP3 blocked Th1 differentiation in vitro. Mice models of delayed type hypersensitivity (DTH) reactions were generated by subcutaneous sensitization and challenge with ovalbumin (OVA) to the ears of mice. PTD mFOXP3, which was administered via local subcutaneous injection, significantly reduced DTH induced inflammation, including ear swelling (ear swelling, P<0.001; pinnae weight, P<0.05 or P<0.01 with 0.25 and 1.25 mg/kg PTD mFOXP3, respectively), infiltration of T cells, and expression of interferon γ at local inflammatory sites (mRNA level P<0.05) compared with the DTH group. The results of the present study demonstrated that PTD mFOXP3 may attenuate DTH reactions by suppressing the infiltration and activity of Th1 cells.