Abstract
Background: Kidney transplantation (KTx) is a preeminent treatment for end-stage renal disease (ESRD). After the application of immunosuppressants (IS), renal allograft recipients could reach a state called accommodation which means they are neither rejected nor infected. This study aimed to describe the details of this immune accommodation and reveal a novel mechanism of IS on immune cell subpopulations. Methods: We analyzed multiple cell subgroups and their gene expression of peripheral T, B, myeloid, and NK cells from renal allograft recipients with accommodation and healthy control (HC) by single-cell transcriptomics sequencing (scRNA-seq) and flow cytometry. Results: A total of 8,272 cells were isolated and sequenced from three individuals, including 2,758 cells from HC, 2,550 cells from ESRD patient, and 2,964 cells from KTx patient, as well as 396 immune response–related genes were detected during sequencing. 5 T-cell, 4 NK-cell, 5 myeloid, and 4 B-cell clusters were defined. Among them, a B-cell subset (CD19+IGLC3lowIGKChighTCL1A-CD127+) of renal transplant recipients with accommodation was significantly lower than that of HC and verified by flow cytometry, and this B-cell subset showed an activated potential because of its high expression of CD127. Furthermore, we found that IL32 might be the key cytokine to induce the differentiation of this B-cell cluster. Conclusion: We found a novel B-cell subset (CD19+IGLC3lowIGKChighTCL1A-CD127+) which was inhibited and decreased in renal allograft recipients with accommodation. This study might reveal the effect of commonly used IS in clinical practice on B-cell subsets and related mechanism.
Highlights
Kidney transplantation (KTx) is a preeminent treatment for end-stage renal disease (ESRD) (Parajuli et al, 2018) that effectively improves the quality of life of patients undergoing dialysis
We reported that multiple subpopulations of B cells were altered in renal allograft recipients with accommodation, including reduced levels of regulatory B cells (Bregs) (CD38highCD27+CD24+), transitional B cells (IgM+CD38highCD24high), and marginal zone (MZ) B cells but increased levels of IgD-CD27+ and CD38lowCD21- B cells (Zhuang et al, 2020)
T cells are often regarded as the target cells of immunosuppressive agents (Lim et al, 2017), but in our data, B cells, not T cells, were obviously suppressed in the KTx group compared with the healthy controls (HC) group (Figure 1G)
Summary
Kidney transplantation (KTx) is a preeminent treatment for end-stage renal disease (ESRD) (Parajuli et al, 2018) that effectively improves the quality of life of patients undergoing dialysis. IS commonly used in the clinic (i.e., FK506, mycophenolate mofetil (MMF), and steroids) target the activation and proliferation of T cells (Romano et al, 2019). It is not clear whether these IS could affect other immune cells, such as B cells, NK cells, and myeloid cells. After the application of immunosuppressants (IS), renal allograft recipients could reach a state called accommodation which means they are neither rejected nor infected. This study aimed to describe the details of this immune accommodation and reveal a novel mechanism of IS on immune cell subpopulations
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