Objective: Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease that commonly affects the kidney. Single-cell RNA sequencing (scRNA-seq) technology is a powerful tool for characterizing individual cells and elucidating biological mechanisms at the cellular level. The purpose of this study was to identify the mechanism underlying kidney injury in SLE using scRNA-seq technology.
Methods: scRNA-seq data of peripheral blood mononuclear cells (PBMCs) in SLE were retrieved from the GEO database, followed by batch effect elimination, dimensionality reduction, cluster analysis, cell annotation and enrichment analysis. A model of SLE was developed in NZB/WF1 mice. Effects of anti-CD45RB antibody on the SLE-induced kidney injury were evaluated, and we measured the distribution of regulatory T cells and B cells in mouse spleen and kidney tissues, levels of kidney function-related indexes, deposition of IgG and C3 in the glomeruli, and the levels of inflammatory cytokines.
Results: CD45RB was a specific marker gene of B cell clusters and had influence on the B cells. anti-CD45RB antibody treatment induced regulatory B cells and consequently arrested the kidney injury caused by SLE. In addition, depletion of regulatory T cells was found to partially undermine the alleviatory effect of anti-CD45RB antibody on SLE-induced kidney injury.
Conclusion: Collectively, our data suggest that anti-CD45RB antibody can prevent the SLE-induced kidney injury, pointing to anti-CD45RB antibody as a potential therapeutic strategy in kidney injury-related disease.
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http://dx.doi.org/10.1016/j.jaut.2022.102949 | DOI Listing |
J Autoimmun
January 2023
Department of Rheumatology, The First Hospital of Jilin University, No. 1 Xinmin Street, Changchun, 130021, China. Electronic address:
Objective: Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease that commonly affects the kidney. Single-cell RNA sequencing (scRNA-seq) technology is a powerful tool for characterizing individual cells and elucidating biological mechanisms at the cellular level. The purpose of this study was to identify the mechanism underlying kidney injury in SLE using scRNA-seq technology.
View Article and Find Full Text PDFXenotransplantation
November 2022
Department of Gastrointestinal Surgery, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
Background: The treatment of diabetes by islet cell transplantation has become an accepted therapy, with transplantation of xenogeneic islet cells an attractive alternative to the problem. Previous studies in mice have demonstrated that anti-CD45RB induce immune tolerance in human pancreatic islet cells. The current study was to define the mechanism of action of anti-CD45RB induced nonspecific immune tolerance to heteroantigens.
View Article and Find Full Text PDFJCI Insight
October 2021
Ian Burr Division of Endocrinology and Diabetes, Department of Pediatrics.
Autoimmune disease has presented an insurmountable barrier to restoration of durable immune tolerance. Previous studies indicate that chronic therapy with metabolic inhibitors can reduce autoimmune inflammation, but it remains unknown whether acute metabolic modulation enables permanent immune tolerance to be established. In an animal model of lupus, we determined that targeting glucose metabolism with 2-deoxyglucose (2DG) and mitochondrial metabolism with metformin enables endogenous immune tolerance mechanisms to respond to tolerance induction.
View Article and Find Full Text PDFBackground: Regulatory B cells are a newly discovered B cell subset that suppresses immune responses. Recent studies found that both anti-CD45RB and anti-Tim-1 treatments regulate immune responses by inducing regulatory B cells; however, the role of these cells in renal ischemia-reperfusion injury (IRI) is unknown.
Methods: Using mouse models, including T cell-deficient (RAG1 knockout and TCR knockout) mice and B cell-deficient (MT) mice, we investigated the effects of regulatory B cells and anti-CD45RB on IRI and the mechanisms underlying these effects.
Transplant Proc
December 2018
School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan Province, China; Sichuan Provincial Key Laboratory for Translational Medicine of Organ Transplantation, Chengdu, Sichuan Province, China; Department of Gastrointestinal Surgery, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, Sichuan Province, China.
Background: Our previous study demonstrated that regulatory B cells (Bregs) play an indispensable role in dual anti-CD45RB/anti-TIM-1 antibody-induced transplantation tolerance through an IL-10-dependent pathway. However, the potentially specific subsets of Bregs have not been clearly demonstrated. In this study, we aimed to detect the subsets of the Bregs possessing the ability to produce IL-10 in the early stage and tolerance maintenance stage of allogeneic islet transplantation treated by dual anti-CD45RB/anti-TIM-1.
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