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

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

doi:10.1016/j.xinn.2024.100599

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

Innovation (Camb). 2024 Mar 1;5(3):100599. doi: 10.1016/j.xinn.2024.100599. eCollection 2024 May 6.

Authors

Rui Wang^{1

2}, Xiao Peng^{1

2}, Yixin Yuan^{1

2}, Baojie Shi^{1

2}, Yuan Liu³, Hengxiao Ni⁴, Wenzhi Guo⁵, Qiwei Yang⁴, Pingguo Liu⁶, Jie Wang^{1

2}, Zhaojie Su^{1

2}, Shengnan Yu^{1

2}, Dehua Liu^{1

2}, Jinyan Zhang³, Junjie Xia^{1

2}, Xueni Liu³, Hao Li^{1

2}, Zhengfeng Yang⁷, Zhihai Peng^{1

2}

Affiliations

¹ Organ Transplantation Clinical Medical Center of Xiamen University, Department of General Surgery, Xiang'an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361102, China.
² Organ Transplantation Institute of Xiamen University, Xiamen Human Organ Transplantation Quality Control Center, Xiamen Key Laboratory of Regeneration Medicine, Fujian Provincial Key Laboratory of Organ and Tissue Regeneration, School of Medicine, Xiamen University, Xiamen 361102, China.
³ Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.
⁴ State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen 361102, China.
⁵ Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450000, China.
⁶ Department of Hepatobiliary & Pancreatic Surgery, The National Key Clinical Specialty, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361102, China.
⁷ Precision Research Center for Refractory Diseases, Institute for Clinical Research, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201620, China.

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, 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.