Dissecting the immune discrepancies in mouse liver allograft tolerance and heart/kidney allograft rejection

  • Jun Pan 1 ,
  • Fang Ye , 2,3 ,
  • Hui Li 4 ,
  • Chengxuan Yu 3 ,
  • Jiajia Mao 5 ,
  • Yanyu Xiao 3 ,
  • Haide Chen 3 ,
  • Junqing Wu 3 ,
  • Jiaqi Li 3 ,
  • Lijiang Fei 3 ,
  • Yijun Wu , 1 ,
  • Xiaoming Meng , 6 ,
  • Guoji Guo , 2,3,7 ,
  • Yingying Wang , 5
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  • 1. Department of Thyroid Surgery, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
  • 2. Liangzhu Laboratory, Zhejiang University, Hangzhou, China
  • 3. Center for Stem Cell and Regenerative Medicine and Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
  • 4. Key Laboratory of Combined Multiorgan Transplantation, Ministry of Public Health, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
  • 5. Kidney Disease Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
  • 6. Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, The Key Laboratory of Anti-inflammatory of Immune Medicines, Ministry of Education, Hefei, China
  • 7. Zhejiang Provincial Key Lab for Tissue Engineering and Regenerative Medicine, Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine, Hangzhou, Zhejiang, China
ye-fang@zju.edu.cn
wuwu5925@zju.edu.cn
mengxiaoming@ahmu.edu.cn
ggj@zju.edu.cn
cynthia.w@163.com

Received date: 04 Jun 2023

Revised date: 23 Aug 2023

Accepted date: 15 Sep 2023

Copyright

2023 2023 The Authors. Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd.

Abstract

The liver is the most tolerogenic of transplanted organs. However, the mechanisms underlying liver transplant tolerance are not well understood. The comparison between liver transplantation tolerance and heart/kidney transplantation rejection will deepen our understanding of tolerance and rejection in solid organs. Here, we built a mouse model of liver, heart and kidney allograft and performed single-cell RNA sequencing of 66,393 cells to describe the cell composition and immune cell interactions at the early stage of tolerance or rejection. We also performed bulk RNA-seq of mouse liver allografts from Day 7 to Day 60 post-transplantation to map the dynamic transcriptional variation in spontaneous tolerance. The transcriptome of lymphocytes and myeloid cells were characterized and compared in three types of organ allografts. Cell–cell interaction networks reveal the coordinated function of Kupffer cells, macrophages and their associated metabolic processes, including insulin receptor signalling and oxidative phosphorylation in tolerance induction. Cd11b+ dendritic cells (DCs) in liver allografts were found to inhibit cytotoxic T cells by secreting anti-inflammatory cytokines such as Il10. In summary, we profiled single-cell transcriptome analysis of mouse solid organ allografts. We characterized the immune microenvironment of mouse organ allografts in the acute rejection state (heart, kidney) and tolerance state (liver).

Cite this article

Jun Pan , Fang Ye , Hui Li , Chengxuan Yu , Jiajia Mao , Yanyu Xiao , Haide Chen , Junqing Wu , Jiaqi Li , Lijiang Fei , Yijun Wu , Xiaoming Meng , Guoji Guo , Yingying Wang . Dissecting the immune discrepancies in mouse liver allograft tolerance and heart/kidney allograft rejection[J]. Cell Proliferation, 2024 , 57(3) : e13555 . DOI: 10.1111/cpr.13555

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