鲁索利替尼
免疫系统
CD8型
免疫学
细胞毒性T细胞
下调和上调
癌症研究
移植
医学
T细胞
生物
内科学
骨髓
体外
基因
生物化学
骨髓纤维化
作者
Yuan Chang,Mengda Xu,Yuxin Zhang,Xiaohong Chen,Yixuan Sheng,Menghao Tao,Martin E. Schimpf,Zhenyu Xu,Shengshou Hu,Jiangping Song
标识
DOI:10.1016/j.clim.2023.109851
摘要
The benefits of IL2RA antagonists in heart transplant patients are controversial. We aimed to elucidate the effects of IL2RA antagonists and identify targets that could be better than IL2RA antagonists. By using single-cell RNA sequencing of immune cells at different time points in patients receiving IL2RA antagonists, we identified nineteen types of cells. We revealed higher IL2RA expression in regulatory T cells (Tregs), suggesting that IL2RA antagonists attenuated IL-2-induced Treg activation. CD4_C04_IFNGR1 and CD8_C05_IFITM2 which had more cytotoxic effects, remained elevated at later time points. IFNGR1 was upregulated in these two subtypes, but was not expressed in Treg. Ruxolitinib targeted the pathways of IFNGR1 (JAK1/2) while not affecting the pathway of IL-2-induced Tregs activation (JAK3). Ruxolitinib showed prolonged survival compared to IL2RA mAb-treated mice. Our study provided dynamic changes of immune cells after IL2RA antagonists treatment at single-cell resolution. Ruxolitinib has potential as a new immunoinduction therapy without affecting Treg.
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