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Single-cell transcriptomics of peripheral blood reveals a novel B-cell subset in renal allograft recipients with accommodation

ABSTRACT: Kidney transplantation is a preeminent treatment for end-stage renal disease . The application of immunosuppressants is needed for kidney recipients to avoid allograft rejection but increase the risk of infection, and balance between rejection and infection is an important in clinical to reach the immune accommodation. Here, we use single-cell RNA sequencing to fully assess the immune status of peripheral mononuclear cells in kidney recipients. and compared the differences between kidney recipients and healthy people to describe the characteristics of the immune accommodation of kidney recipients. We found a novel B cell subset (CD19+IGKC+IGLC3lowTCL1A-CD127+) of renal transplant recipients with accommodation was significantly lower than that of healthy people and verified by flow cytometry. which may have potential regulatory potential. Furthermore, we found that IL32 may increase the expression of CD19+IGKC+IGLC3lowTCL1A-CD127+ Bcells. In summary, we found that the CD19+IGKC+IGLC3lowTCL1A-CD127+B subgroup with immunomodulatory potential is inhibited in kidney recipients with accommodation state, and IL-32 has therapeutic potential for this.

ORGANISM(S): Homo sapiens

PROVIDER: GSE175429 | GEO | 2021/05/25

REPOSITORIES: GEO

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Project description:Objective: Apolipoprotein E (Apo E) is a multifunctional protein, originally described in the context of lipoprotein metabolism and cardiovascular disease. More recently, anti-inflammatory functions of ApoE have been documented. ApoE was studied in the context of several inflammatory disorders, but its role in the pathogenesis of acute organ rejection is unknown. In this study, we test the hypothesis that ApoE attenuates acute renal allograft rejection. Materials and methods: The Dark Agouti (DA) to Lewis (Lew) and the Brown Norway (BN) to Lew rat strain combinations were used to investigate fatal acute rejection. In addition, Fischer 344 (F344) kidneys were transplanted to Lew rats to study reversible acute rejection. Isograft recipients and untreated Lew rats were used as controls. ApoE mRNA expression was quantified in intravascular leukocytes accumulating in the blood vessels of renal grafts and in graft tissue. Apo E protein levels were assessed in blood plasma. To test the protective potential of ApoE, recipients of BN kidneys were treated with ApoE-mimetic peptide. Results: Intravascular graft leukocytes and renal tissue obtained from animals undergoing reversible acute rejection expressed increased levels of ApoE mRNA, whereas during fatal rejection, ApoE expression remained unchanged in the BN to Lew rat strain combination or was significantly reduced when DA rats were used as donors of the kidney. On the protein level, no changes in ApoE were seen in plasma. However, we do not know if local leukocytic ApoE expression results in increased ApoE concentrations inside graft blood vessels. Peptide treatment of allograft recipients reversed fatal rejection and significantly improved animal survival. Conclusions: ApoE plays a protective role in acute organ rejection. Further studies are needed to understand the exact mechanism how ApoE reverses acute rejection. dual-color balanced dye-swap design with 4 biological replicates, hybridized on 4 arrays

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Single-cell transcriptomics of peripheral blood reveals a novel B-cell subset in renal allograft recipients with accommodation

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