Abstract
Allograft rejection is a common immunological feature in renal transplantation and is associated with reduced graft survival. A mouse renal allograft rejection model was induced and single-cell RNA sequencing (scRNA-seq) data of CD45+ leukocytes in kidney allografts on days 7 (D7) and 15 (D15) after operation was analyzed to reveal a full immunological profiling. We identified 20 immune cell types among 10,921 leukocytes. Macrophages and CD8+ T cells constituted the main populations on both timepoints. In the process from acute rejection (AR) towards chronic rejection (CR), the proportion of proliferating and naïve CD8+ T cells dropped significantly. Both B cells and neutrophils decreased by about 3 folds. On the contrary, the proportion of macrophages and dendritic cells (DCs) increased significantly, especially by about a 4.5-fold increase in Ly6cloMrc1+ macrophages and 2.6 folds increase in Ly6cloEar2+ macrophages. Moreover, myeloid cells harbored the richest ligand and receptor (LR) pairs with other cells, particularly for chemokine ligands such as Cxcl9, Cxcl10, Cxcl16 and Yars. However, macrophages with weak response to interferon gamma (IFNg) contributed to rejection chronicization. To conclude, reduction in CD8 T cells, B cells and neutrophils while increasing in Ly6cloMrc1+ macrophages and Ly6cloEar2+ macrophages, may contribute significantly to the progress from AR towards CR.
Highlights
Rejection of the transplanted kidney in humans is still a major cause of morbidity and mortality
Blood was collected in serum separator tube by cardiac puncture from WT C57Bl6/J mice, kidney allograft recipients sacrificed on days 7 (D7) and D15 after kidney transplantation
Histological features of kidney allografts from WT and kidney allograft recipient mice were examined by hemotoxylin & eosin (HE), periodic acid–Schiff (PAS) and Masson staining (Figure 1A)
Summary
Rejection of the transplanted kidney in humans is still a major cause of morbidity and mortality. Due to unpredictability of tissue availability, limited size of kidney biopsy samples, challenges are raised in wide application of scRNA-seq to dissect immunological network and dynamic changes involved in human kidney allograft rejection. Studying the evolution of the pathology of rejection in mouse kidney allografts, interstitial infiltrate, major histocompatibility complex (MHC) induction, and venulitis peaked at day 7-10, stabilized or regressed by day 21 [8]. By scRNA-seq, immune cells isolated from allografts undergoing AR on D7 to CR on D15 following kidney transplantation should gain new insights into the immunological profiling, dynamic changes from AR to CR during renal transplant rejection
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