Long-term CXCR3 antagonist AMG487 mitigated acute graft-versus-host disease by inhibiting T cell activation in a murine model

IF 1.6 4区医学 Q4 IMMUNOLOGY

Transplant immunology Pub Date : 2024-09-12 DOI:10.1016/j.trim.2024.102128

Miao Shengchao , Tang Bo , Liu Huihui , Qin Chenchen , Liu Beichen , Wang Zhenhua , Ma Ning , Shi Yongjin

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引用次数: 0

Abstract

Background

Lymphocyte migration plays a key role in the development of acute graft-versus-host disease (aGVHD). Blocking lymphocyte migration by targeting chemokine receptors, such as CXCR3, may be a promising strategy for preventing and treating aGVHD. Our previous studies have shown that short-term CXCR3 antagonist treatment combined with cyclosporine A alleviated aGVHD. However, the effect of long-term AMG487 treatment on aGVHD survival has not been thoroughly investigated.

Methods

A murine aGVHD model was used to examine the expression of CXCR3 in donor T cells. The effects of short- and long-term AMG487 treatment on aGVHD survival were assessed. The infiltration of donor T cells into the liver and spleen tissues and the activation of donor T cells in splenic tissues were also examined.

Results

CXCR3 was consistently highly expressed in donor T cells in a murine aGVHD model. Long-term AMG487 treatment, but not short-term, improved survival and aGVHD outcomes (p < 0.05). Furthermore, long-term AMG487 administration reduced the number of donor T cells in the liver but increased the number of donor T cells in the spleen (p < 0.05). Long-term AMG487 treatment also inhibited donor T cell activation in the spleen (p < 0.05).

Conclusion

This study demonstrates that long-term AMG487 treatment has a potential therapeutic effect on aGVHD and could be used as a novel therapy.

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通过抑制小鼠模型中T细胞的活化，长期使用CXCR3拮抗剂AMG487可缓解急性移植物抗宿主疾病

背景淋巴细胞迁移在急性移植物抗宿主病（aGVHD）的发生中起着关键作用。通过靶向趋化因子受体（如CXCR3）阻断淋巴细胞迁移可能是预防和治疗移植物抗宿主疾病的一种有效策略。我们之前的研究表明，短期CXCR3拮抗剂治疗联合环孢素A可减轻aGVHD。方法用小鼠 aGVHD 模型检测供体 T 细胞中 CXCR3 的表达。评估了短期和长期 AMG487 治疗对 aGVHD 存活率的影响。结果在小鼠 aGVHD 模型中，供体 T 细胞中的 CXCR3 始终高表达。长期 AMG487 治疗（而非短期）可改善存活率和 aGVHD 结果（p < 0.05）。此外，长期服用AMG487会减少肝脏中供体T细胞的数量，但会增加脾脏中供体T细胞的数量（p <0.05）。结论这项研究表明，长期 AMG487 治疗对 aGVHD 有潜在的治疗作用，可作为一种新型疗法。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Transplant immunology 医学-免疫学

CiteScore

2.10

自引率

13.30%

发文量

198

审稿时长

48 days

期刊介绍： Transplant Immunology will publish up-to-date information on all aspects of the broad field it encompasses. The journal will be directed at (basic) scientists, tissue typers, transplant physicians and surgeons, and research and data on all immunological aspects of organ-, tissue- and (haematopoietic) stem cell transplantation are of potential interest to the readers of Transplant Immunology. Original papers, Review articles and Hypotheses will be considered for publication and submitted manuscripts will be rapidly peer-reviewed and published. They will be judged on the basis of scientific merit, originality, timeliness and quality.