Dynamic immune recovery process after liver transplantation revealed by single-cell multi-omics analysis

IF 33.2 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES
Rui Wang, Xiao Peng, Yixin Yuan, Baojie Shi, Yuan Liu, Hengxiao Ni, Wenzhi Guo, Qiwei Yang, Pingguo Liu, Jie Wang, Zhaojie Su, Shengnan Yu, Dehua Liu, Jinyan Zhang, Junjie Xia, Xueni Liu, Hao Li, Zhengfeng Yang, Zhihai Peng
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Abstract

Elucidating the temporal process of immune remodeling under immunosuppressive treatment after liver transplantation (LT) is critical for precise clinical management strategies. Here, we performed a single-cell multi-omics analysis of peripheral blood mononuclear cells (PBMCs) collected from LT patients (with and without acute cellular rejection (ACR)) at 13 time points. Validation was performed in two independent cohorts with additional LT patients and healthy controls. Our study revealed a four-phase recovery process after LT and delineated changes in immune cell composition, expression programs, and interactions along this process. The intensity of the immune response differs between the ACR and non-ACR patients. Notably, the newly identified inflamed NK cells, CD14RNASE2 monocytes, and FOS-expressing monocytes emerged as predictive indicators of ACR. This study illuminates the longitudinal evolution of the immune cell landscape under tacrolimus-based immunosuppressive treatment during LT recovery, providing a four-phase framework that aids the clinical management of LT patients.
通过单细胞多组学分析揭示肝移植后的动态免疫恢复过程
阐明肝移植(LT)后免疫抑制治疗下免疫重塑的时间过程对于精确的临床管理策略至关重要。在此,我们对13个时间点收集的LT患者(伴有或不伴有急性细胞排斥反应(ACR))的外周血单核细胞(PBMCs)进行了单细胞多组学分析。在两个独立的队列中,对更多的 LT 患者和健康对照组进行了验证。我们的研究揭示了LT术后的四阶段恢复过程,并描述了这一过程中免疫细胞组成、表达程序和相互作用的变化。ACR患者和非ACR患者的免疫反应强度不同。值得注意的是,新发现的发炎 NK 细胞、CD14RNASE2 单核细胞和表达 FOS 的单核细胞成为 ACR 的预测指标。这项研究阐明了在基于他克莫司的免疫抑制治疗下,LT 恢复期免疫细胞的纵向演变,提供了一个四阶段框架,有助于 LT 患者的临床管理。
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来源期刊
The Innovation
The Innovation MULTIDISCIPLINARY SCIENCES-
CiteScore
38.30
自引率
1.20%
发文量
134
审稿时长
6 weeks
期刊介绍: The Innovation is an interdisciplinary journal that aims to promote scientific application. It publishes cutting-edge research and high-quality reviews in various scientific disciplines, including physics, chemistry, materials, nanotechnology, biology, translational medicine, geoscience, and engineering. The journal adheres to the peer review and publishing standards of Cell Press journals. The Innovation is committed to serving scientists and the public. It aims to publish significant advances promptly and provides a transparent exchange platform. The journal also strives to efficiently promote the translation from scientific discovery to technological achievements and rapidly disseminate scientific findings worldwide. Indexed in the following databases, The Innovation has visibility in Scopus, Directory of Open Access Journals (DOAJ), Web of Science, Emerging Sources Citation Index (ESCI), PubMed Central, Compendex (previously Ei index), INSPEC, and CABI A&I.
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