Histone deacetylase inhibitors promote mice corneal allograft survival through alteration of CD4+ effector T cells and induction of Foxp3+ regulatory T cells

• Published in: Cellular immunology 2012-05, Vol.277 (1-2), p.8-13
• Main Authors: Guo, Xuming, Jie, Ying, Ren, Dong, Zeng, Hui, Zhang, Yingnan, He, Yan, Pan, Zhiqiang
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis - drug effects; Cell Proliferation - drug effects; Corneal transplantation; Corneal Transplantation - methods; Down-Regulation - drug effects; Forkhead Transcription Factors - biosynthesis; Foxp3; Graft Survival - drug effects; Histone deacetylase inhibitor (HDACI); Histone Deacetylase Inhibitors - therapeutic use; Hydroxamic Acids - therapeutic use; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Regulatory T cells; T-Lymphocytes, Regulatory - drug effects
• ISSN: 0008-8749; 1090-2163
• DOI: 10.1016/j.cellimm.2012.06.006

► We described the roles of Trichostatin A (TSA) on immuno-modulatory. ► TSA could induce Teff cells apoptosis and inhibit Teff cells proliferation in vitro. ► TSA could up regulate of Foxp3 expression on CD4+ CD25+ T cells in vitro. ► TSA could improve mice corneal allograft survival. ► TSA promoted the proportions and allosuppressive function of Treg cells in vivo. Trichostatin A (TSA) is classical Histone deacetylase inhibitors (HDACIs) II which is used in treatment of advanced cutaneous T-cells lymphoma. Our works focused on the roles of TSA on immuno-modulatory. We found that the TSA could induce resting Teff cells into apoptotic cell death and inhibit Teff cells proliferation in a dose-dependent manner. We also observed down-regulation effects of various costimulatory/adhesion molecules on Teff cells and up-regulation of Foxp3 expression on CD4+ CD25+ T cells. Treatment with TSA could improve mice corneal allograft survival by promoting the proportions and allosuppressive function of CD4+ CD25+ regulatory T cells. Our findings suggest that the use of TSA allows the beneficial pharmacological effect on CD4+ CD25− T activation in vitro and enhancement of Foxp3+ Treg cells in vivo.