Single-Cell Landscape of Mouse Islet Allograft and Syngeneic Graft

Front Immunol. 2022 Jun 10;13:853349. doi: 10.3389/fimmu.2022.853349. eCollection 2022.

Abstract

Islet transplantation to treat the late stage of type 1 diabetic patient (T1DM) has recently made inspiring success in clinical trials. However, most patients experience a decline in islet graft function in one to three years due to immune rejection. Although the mechanisms of immune cells, including macrophages, dendritic cells (DCs), neutrophils, natural killer cells (NKs), B cells, and T cells, that mediate immune rejection have been investigated, the overall characteristics of immune infiltrates in islet allografts and syngeneic grafts remain unclear. Single-cell RNA sequencing (scRNA-seq) has provided us with new opportunities to study the complexity of the immune microenvironment in islet transplants. In the present study, we used scRNA-seq to comprehensively analyze the immune heterogeneity in the mouse model of islet transplantation. Our data revealed T lymphocytes and myeloid cells as the main immune components of grafts 7 days post-islet transplantation, especially in allografts. Moreover, our results indicated that allogeneic islet cells were transformed into antigen-presenting cell-like cells with highly expressed MHC class I molecules and genes involved in MHC class I-mediated antigen presentation. This transformation may dramatically facilitate the interaction with cytotoxic CD8+ T cells and promote the destruction of islet allografts. Our study provides insight into the transcriptomics and diverse microenvironment of islet grafts and their impacts on immune rejection.

Keywords: Beta cell; allograft; diabetes; immune heterogeneity; islet; islet transplantation; single-cell RNA sequencing; the immune atlas.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allografts
  • Animals
  • CD8-Positive T-Lymphocytes*
  • Histocompatibility Antigens Class I
  • Humans
  • Islets of Langerhans Transplantation*
  • Isografts
  • Mice
  • Transplantation, Homologous

Substances

  • Histocompatibility Antigens Class I