Homoharringtonine promotes heart allograft acceptance by enhancing regulatory T cells induction in a mouse model

Autor: Xia Qiu, Hedong Zhang, Zhouqi Tang, Yuxi Fan, Wenjia Yuan, Chen Feng, Chao Chen, Pengcheng Cui, Yan Cui, Zhongquan Qi, Tengfang Li, Yuexing Zhu, Liming Xie, Fenghua Peng, Tuo Deng, Xin Jiang, Longkai Peng, Helong Dai, Yuanyuan Ji
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Chinese Medical Journal, Vol 137, Iss 12, Pp 1453-1464 (2024)
Druh dokumentu: article
ISSN: 0366-6999
2542-5641
00000000
DOI: 10.1097/CM9.0000000000002813
Popis: Abstract. Background:. Homoharringtonine (HHT) is an effective anti-inflammatory, anti-viral, and anti-tumor protein synthesis inhibitor that has been applied clinically. Here, we explored the therapeutic effects of HHT in a mouse heart transplant model. Methods:. Healthy C57BL/6 mice were used to observe the toxicity of HHT in the liver, kidney, and hematology. A mouse heart transplantation model was constructed, and the potential mechanism of HHT prolonging allograft survival was evaluated using Kaplan–Meier analysis, immunostaining, and bulk RNA sequencing analysis. The HHT-T cell crosstalk was modeled ex vivo to further verify the molecular mechanism of HHT-induced regulatory T cells (Tregs) differentiation. Results:. HHT inhibited the activation and proliferation of T cells and promoted their apoptosis ex vivo. Treatment of 0.5 mg/kg HHT for 10 days significantly prolonged the mean graft survival time of the allografts from 7 days to 48 days (P
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