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

• Published in: Transplant immunology Vol. 87; p. 102128
• Main Authors: Shengchao, Miao, Bo, Tang, Huihui, Liu, Chenchen, Qin, Beichen, Liu, Zhenhua, Wang, Ning, Ma, Yongjin, Shi
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.12.2024
• Subjects: Chemokine receptor; CXCR3 antagonist; Graft-versus-host disease; T cells; Graft-versus-host disease; CsA; IFN-γ; CXCR3 antagonist; aGVHD; SYN; Chemokine receptor; T cells; BMMNCs; allo-HSCT
• ISSN: 0966-3274; 1878-5492; 1878-5492
• DOI: 10.1016/j.trim.2024.102128

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 < 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). This study demonstrates that long-term AMG487 treatment has a potential therapeutic effect on aGVHD and could be used as a novel therapy. •AMG487 long-term treatment boosts survival and aGVHD in mice, hinting at therapeutic promise.•AMG487 long-term altered donor T cell distribution: liver infiltration down, spleen T cells up.•AMG487 inhibits spleen donor T cell activation, hints at aGVHD mitigation via immune regulation.