Landscape of Immune Cells Heterogeneity in Liver Transplantation by Single-Cell RNA Sequencing Analysis

• DOI: 10.3389/fimmu.2022.890019
• Publication Date: 2022-05-10T05:20:58Z
• Authors: Xinqiang Li; Shipeng Li; Bin Wu; Qingguo Xu; Dahong Teng; Tongwang Yang; Yandong Sun; Yang Zhao; Tianxiang Li; Dan Liu; Shuang Yang; Weihua Gong; Jinzhen Cai
• Keywords: Sequence Analysis, RNA; MDSC; Immunology; RC581-607; CD8-Positive T-Lymphocytes; liver tranpslant; single cell RNA sequence; Liver Transplantation; 3. Good health; 03 medical and health sciences; 0302 clinical medicine; CD8 T cell; Humans; Transplantation, Homologous; CTLA-4 Antigen; immune; Immunologic diseases. Allergy

Rejection is still a critical barrier to the long-term survival of graft after liver transplantation, requiring clinicians unveil underlying mechanism transplant rejection. The cellular diversity and interplay between immune cells in microenvironment remain unclear. Herein, we performed single-cell RNA sequencing analysis delineate landscape heterogeneity transplantation. T cells, NK B myeloid cell subsets human blood were enriched characterize their tissue distribution, gene expression, functional modules. proportion CCR6+CD4+ increased within an allograft, suggesting that there are more memory CD4+ parallel with exhausted CTLA4+CD8+ actively proliferating MKI67+CD8+ significantly, where they manifested heterogeneity, distinct function, homeostatic proliferation. Remarkably, changes CD1c+ DC, CADM+ MDSC, FOLR3+ Kupffer increase but CD163+ Kupffer, APOE+ GZMA+ decreased. Furthermore, identified LDLR as novel marker activated MDSC prevent Intriguingly, subset CD4+CD8+FOXP3+ included was first detected intercellular communication regulatory implicated LDLR+ interact through TIGIT-NECTIN2 signaling pathway. Taken together, these findings have gained mechanistic insights for understanding it outlines characteristics provides potential therapeutic targets