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

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 ant...

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Veröffentlicht in:Transplant immunology 2024-12, Vol.87, p.102128, Article 102128
Hauptverfasser: Shengchao, Miao, Bo, Tang, Huihui, Liu, Chenchen, Qin, Beichen, Liu, Zhenhua, Wang, Ning, Ma, Yongjin, Shi
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Sprache:eng
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Zusammenfassung: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. 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. 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 
ISSN:0966-3274
1878-5492
1878-5492
DOI:10.1016/j.trim.2024.102128