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

• Published in: Molecular medicine reports Vol. 23; no. 5
• Main Authors: Zhou, Bing, Mei, Fuyang, Wu, Changhao, Xu, Heyun, Liu, Zhifang, Cui, Yong
• Format: Journal Article
• Language: English
• Published: Greece 01.05.2021
• Subjects: Animals; Antigens, CD19 - immunology; Antigens, CD1d - immunology; B-Lymphocytes, Regulatory - drug effects; B-Lymphocytes, Regulatory - immunology; CD5 Antigens - immunology; Cell Count; Cell Lineage - drug effects; Cell Lineage - immunology; Disease Models, Animal; Flow Cytometry; Heart Transplantation; Histone Deacetylase Inhibitors - pharmacology; Humans; Hydroxamic Acids - pharmacology; Immune Tolerance - drug effects; Immune Tolerance - immunology; Mice; Protective Agents - pharmacology
• ISSN: 1791-2997; 1791-3004
• DOI: 10.3892/mmr.2021.11978

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 Breg cells both and . Moreover, TSA treatment increased the frequency of IL‑10 and TGF‑β‑producing CD19 CD5 CD1d Breg cells, and IL‑10 and TGF‑β levels and . 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 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 Breg cells. These results provide a theoretical basis for the prevention of immunological rejection in cardiac transplantation.