Protective effect of trichostatin A on CD19+CD5+CD1dhigh regulatory B cells in heart transplantation

Zhou,Bing; Mei,Fuyang; Wu,Changhao; Xu,Heyun; Liu,Zhifang; Cui,Yong

doi:10.3892/mmr.2021.11978

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

Authors:
- Bing Zhou
- Fuyang Mei
- Changhao Wu
- Heyun Xu
- Zhifang Liu
- Yong Cui
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Affiliations: Department of Cardiothoracic Surgery, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang 310014, P.R. China
Published online on: March 9, 2021 https://doi.org/10.3892/mmr.2021.11978
Article Number: 339

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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.

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