Single-cell RNA-seq revealing the immune features of donor liver during liver transplantation

Abstract

Immune cells, including T and B cells, are key factors in the success of liver transplantation. And the repertoire of T cells and B cells plays an essential function in mechanism of the immune response associated with organ transplantation. An exploration of their expression and distribution in donor organs could contribute to a better understanding of the altered immune microenvironment in grafts. In this study, using single-cell 5’ RNA sequence and single-cell T cell receptor (TCR)/B cell receptor (BCR) repertoire sequence, we profiled immune cells and TCR/BCR repertoire in three pairs of donor livers pre- and post-transplantation. By annotating different immune cell types, we investigated the functional properties of monocytes/Kupffer cells, T cells and B cells in grafts. Bioinformatic characterization of differentially expressed genes (DEGs) between the transcriptomes of these cell subclusters were performed to explore the role of immune cells in inflammatory response or rejection. In addition, we also observed shifts in TCR/BCR repertoire after transplantation. In conclusion, we profiled the immune cell transcriptomics and TCR/BCR immune repertoire of liver grafts during transplantation, which may offer novel strategies for monitoring recipient immune function and treatment of rejection after liver transplantation.

Antigen-driven CD8+T cell clonal expansion is a prominent feature of MASH in humans and mice

“…Figure 1D,E). Utilizing known markers of T cell functional state, we were able to identify multiple subsets of T cell populations including two clusters of Naïve/central memory (Tcm) ( SELL, CCR7, CD27, IL7R, LTB, and LEF1 ), four clusters of resident memory (Trm) ( IL7R and CD69) , twelve clusters of effector/effector memory (Tem) ( NKG7, GZMA, GZMB, CCL4, and XCL1) , three clusters of gamma delta (γδ) T cells ( TCRD) , and single clusters of T helper 17 (Th17) ( TIMP1, RORC ), T-regulatory cells (Treg) ( FOXP3, IL2RA, CTLA4 ), TEM re-expressing CD45RA (Temra) ( NKG7, GZMK, CX3CR1 ), and mucosal-associated invariant T cells (MAIT) ( ZBTB16, SLC4A10, TRAV1-2 ) (Figure 1C,D) 36,37 . Unsurprisingly, liver resident T cells had a significantly different transcriptional profile from T cells isolated from peripheral blood, with liver resident T cells being almost exclusively contained in the CD8 + Trm, Tem, and Temra clusters and PBMC T cells being highly enriched for Naïve/Tcmand CD4 + clusters (Figure 1E).…”

Updates on the Immune Cell Basis of Hepatic Ischemia-Reperfusion Injury

“…In human liver donors, transcriptome profiling of intrahepatic cells revealed the dynamic changes of the transcriptome in immune cell clusters, particularly in mononuclear phagocytes ( Wang et al, 2021a ). Likely, scRNA-seq, as well as T/B cell receptor repertoire sequencing of human transplanted livers, successfully generated a single-cell atlas of various immune cells such as macrophages, T/B lymphocytes, and NK/NKT cells ( Shan et al, 2023 ). These studies provide an up-to-date collective image of immune cell dynamics during liver transplantation and hepatic IRI.…”

“…In addition, pharmacological targeting of RNAase activity of endoplasmic reticulum stress sensor in KC reduces unfolded protein response and attenuates inflammatory damage during hepatic IRI ( Cai et al, 2022 ). Furthermore, co-culturing with mesenchymal stem cells restrains M1 macrophage polarization, whereas boosts M2 polarization potentially through the control of mitochondrial homeostasis, attenuating liver IRI ( Shang et al, 2023 ).…”

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

“… 5 However, these studies were conducted in animal LT models and may not reflect the dynamics in LT patients. Several single-cell studies of intrahepatic immune cells in LT patients have been published, 5 , 6 , 7 but data were only gathered for limited time points. Other studies used CyTOF or T cell receptor repertoire analyses to address the alterations in immune cells among LT patients but with limited cell markers.…”