Protective effect of trichostatin A on CD19⁺CD5⁺CD1d^high regulatory B cells in heart transplantation

Abstract

Heart transplantation is widely used for the treatment of several heart diseases. Regulatory B cells (Breg cells) serve a critical role in immune tolerance. However, the role of Breg cells in immune tolerance in the context of allogeneic heart transplantation remains poorly understood. The present study aimed to explore the effect of histone deacetylase (HDAC) inhibitor trichostatin A (TSA)-regulated Breg on the regulation of immune tolerance in heart transplantation. By constructing anallogeneic heart transplantation mouse model, and performing flow cytometry, reverse transcription-quantitative PCR, western blotting and carboxyfluorescein succinimidyl esterstaining assays, TSA-regulated Breg cells and their effects on immune tolerance in heart transplantation were evaluated. The results demonstrated that TSA increased the frequency of CD19 + CD5 + CD1d high Breg cells both in vitro and in vivo. Moreover, TSA treatment increased the frequency of IL-10 and TGF-β-producing CD19 + CD5 + CD1d high Breg cells, and IL-10 and TGF-β levels in vitro and in vivo. TSA administration significantly prolonged the survival rate in a heart transplant experiment model. In addition, the IL-10 inhibitor ammonium trichloro(dioxoethylene-o,o')tellurate partially reduced the survival rate and the percentages of CD19 + CD5 + CD1d high Breg cells in mice receiving heart allografts. In contrast, anti-CD20 treatment significantly decreased the survival rate in these mice. Collectively, the present findings suggested that TSA may induce immune tolerance following heart transplantation by regulating CD19 + CD5 + CD1d high Breg cells. These results provide a theoretical basis for the prevention of immunological rejection in cardiac transplantation.

Epigenetic regulation of B cells and its role in autoimmune pathogenesis

“…Entinostat, an HDAC inhibitor, inhibits the binding of HDAC1 to the promoter region of Il10 and promotes the induction of IL-10-producing B cells by LPS [ 120 ]. Another HDAC inhibitor, trichostatin A, increases the frequency of IL‑10- and TGF‑β‑producing CD5 + CD1d high B cells in vitro and in vivo [ 121 ], suggesting that HDAC inhibitors might be potential agents for treating autoimmune diseases and transplant rejection. SCFAs from the environment not only epigenetically regulate the generation of GC B cells and plasma cells but also promote IL-10 expression dependent on their HDAC inhibitory activity [ 70 , 122 ].…”