时空单细胞分析揭示了人体移植与宿主疾病中的T细胞克隆动力学和表型塑性
bioRxiv : the preprint server for biology
|June 12, 2025
概括
移植与宿主疾病 (GVHD) 涉及T细胞扩张. 新的计算工具揭示了T细胞程序和肠道免疫细胞变化如何与GVHD严重程度相关,为治疗提供了洞察力.
科学领域:
- 免疫学 免疫学 免疫学
- 血液学 血液学 血液学
- 计算生物学 计算生物学
背景情况:
- 全基性造血细胞移植 (alloHCT) 提供了治疗血液病的方法,但也带来了急性移植对宿主疾病 (GVHD) 的风险.
- GVHD是一种复杂的T细胞介导病理,需要更深入的理解,以改善患者的治疗结果.
研究的目的:
- 使用多组学方法剖析急性GVHD的T细胞介导病理.
- 确定T细胞克隆扩展程序及其与GVHD严重程度和临床结果的关联.
- 调查肠内免疫细胞在GVHD病变发生中的作用.
主要方法:
- 移植前全活性T细胞鉴定与血液和肠道的纵向跟踪的整合.
- 利用基于混合淋巴细胞反应的克隆指纹,TCR克隆类型和单细胞RNA/TCR测序.
- 采用DecompTCR,这是一种用于纵向TCR分析的新型计算工具,以及肠道活检的空间转录组学.
主要成果:
- 确定了与GVHD严重程度和临床结果相关的动态克隆扩展程序.
- 在GVHD期间,肠道中发现了CD8+效应体和ZNF683 (((Hobit) +居民记忆T细胞的丰富和扩张.
- 已证明CD8+效应T细胞在肠干细胞附近的局部化,与上皮损伤相关.
结论:
- 该研究定义了GVHD中的动态免疫电路重新连接和表型可塑性.
- 这些发现对开发新的生物标志物和GVHD的治疗策略有影响.
- 突出了综合多组学和计算工具用于剖析复杂免疫反应的实用性.
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