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

• Published in: Innovation (New York, NY) Vol. 5; no. 3; p. 100599
• Main Authors: Wang, Rui, Peng, Xiao, Yuan, Yixin, Shi, Baojie, Liu, Yuan, Ni, Hengxiao, Guo, Wenzhi, Yang, Qiwei, Liu, Pingguo, Wang, Jie, Su, Zhaojie, Yu, Shengnan, Liu, Dehua, Zhang, Jinyan, Xia, Junjie, Liu, Xueni, Li, Hao, Yang, Zhengfeng, Peng, Zhihai
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 06.05.2024; Elsevier
• ISSN: 2666-6758; 2666-6758
• DOI: 10.1016/j.xinn.2024.100599

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, CD14+RNASE2+ 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. [Display omitted] •A dynamic immune landscape after liver transplantation unveils a four-phase recovery process, facilitating the precise management of liver transplantation patients.•T cell activity deficiency does not completely suppress the allogeneic cell rejection.•The elevated proportion of inflamed NK cell subset is a potential driver for graft rejection in liver transplantation patients.•Monocytes serve as the major signal source to initialize immune responses after liver transplantation.•CD14+RNASE2+ monocytes and FOS-expressing monocytes are potential early predictive indicators for graft rejection.