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Long Term Intravital Multiphoton Microscopy Imaging of Immune Cells in Healthy and Diseased Liver Using CXCR6.Gfp Reporter Mice
Published on: March 24, 2015
Dynamic immune recovery process after liver transplantation revealed by single-cell multi-omics analysis
Rui Wang1,2, Xiao Peng1,2, Yixin Yuan1,2
1Organ 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.
Insights
This study reveals a four-phase immune recovery after liver transplantation (LT), identifying key immune cell changes and predictive markers for acute cellular rejection (ACR) under immunosuppression.
Area of Science:
- Immunology
- Transplantation Medicine
- Genomics
Background:
- Understanding immune system recovery after liver transplantation (LT) is crucial for managing immunosuppressive therapy and preventing rejection.
- Acute cellular rejection (ACR) remains a significant complication impacting graft survival and patient outcomes.
Purpose of the Study:
- To elucidate the temporal dynamics of immune cell remodeling following LT under immunosuppressive treatment.
- To identify immune cell signatures that can predict or indicate acute cellular rejection (ACR).
Main Methods:
- Single-cell multi-omics analysis of peripheral blood mononuclear cells (PBMCs) from LT patients at 13 time points.
- Validation in two independent cohorts including LT patients and healthy controls.
- Longitudinal tracking of immune cell composition, gene expression, and cellular interactions.
Main Results:
- A distinct four-phase immune recovery process was identified post-LT.
- Significant differences in immune response intensity were observed between ACR and non-ACR patients.
- Inflamed NK cells, CD14+RNASE2+ monocytes, and FOS-expressing monocytes were identified as predictive indicators of ACR.
Conclusions:
- The study provides a four-phase framework for understanding immune evolution after LT under tacrolimus-based immunosuppression.
- Identified immune cell populations offer potential biomarkers for early detection of ACR.
- Findings can inform personalized clinical management strategies for LT recipients.
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.
