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PD-1-PD-L1 Axis Activation Suppresses CD8+ T Cells and Improves Nephritis [scRNA-seq, scTCR-seq]

ABSTRACT: To dissect whether PD-1+CD8+ T cells are exhausted in lupus nephritis, scRNA-seq were performed to define the heterogeneous and pathologic subset.

ORGANISM(S): Mus musculus

PROVIDER: GSE228812 | GEO | 2023/04/18

REPOSITORIES: GEO

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PD-1-PD-L1 Axis Activation Suppresses CD8+ T Cells and Improves Nephritis [RNA-seq]

Project description:PD-1+CD8+ T cells are exhausted in infection and cancer, their roles in lupus nephritis (LN) are largely unknown. PD-1+CD8+ and PD-1-CD8+ cells from spleens of NZB/W F1 mice were sorted for RNA-seq.

2023-04-18 | GSE228811 | GEO

Heterogeneity and Clonality of Kidney-infiltrating T cells in Murine Lupus Nephritis.

Project description:Purpose:We previously found that kidney-infiltrating T cells (KITs) in murine lupus nephritis (LN) resembled dysfunctional T cells that infiltrate tumors. This unexpected finding raised the question of how to reconcile the “exhausted” phenotype of KITs with ongoing tissue destruction in LN. Methods: we performed scRNA-seq and TCR-seq of KITs in murine lupus models using 10X Genomics Chromium system . Results: We found that CD8 KITs exist first in a transitional state, before clonally expanding and evolving toward exhaustion. On the other hand, CD4 KITs did not fit into current differentiation paradigms, but included both hypoxic and cytotoxic subsets with a pervasive exhaustion signature. Thus, autoimmune nephritis is unlike acute pathogen immunity; rather the kidney microenvironment suppresses T cells by progressively inducing exhausted states. Our findings suggest that lupus nephritis, a chronic condition, results from slow evolution of damage caused by dysfunctional T cells and their precursors on the way to exhaustion. These findings have implications for both autoimmunity and tumor immunology.

2022-02-24 | GSE197339 | GEO

PD-1-PD-L1 Axis Activation Suppresses CD8+ T Cells and Improves Nephritis [scRNA-seq, scTCR-seq]

Project description:PD-1-PD-L1 Axis Activation Suppresses CD8+ T Cells and Improves Nephritis [scRNA-seq, scTCR-seq]

| PRJNA951677 | ENA

PD-1-PD-L1 Axis Activation Suppresses CD8+ T Cells and Improves Nephritis.

Project description:PD-1-PD-L1 Axis Activation Suppresses CD8+ T Cells and Improves Nephritis.

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Effect of Sirolimus treatment on lupus nephritis in NZB/W F1 female mice

Project description:NZB/WF1 female mice spontaneously develop autoimmune lupus nephritis. Expression profiling of kidney tissue from (a) 12 week NZB/W F1 female mice defined as asymptomatic for lupus nephritis, (b) 36 and 42 week NZB/W F1 female mice defined as diseased/symptomatic for lupus nephritis and (c) 36 and 42 week NZB/W F1 female mice that are diseased/symptomatic for lupus nephritis and treated with Sirolimus was carried out. The goal of the study was to identify genes associated with lupus nephritis and modulated by Sirolimus, an inhibitor of mTOR. In addition, lupus nephritis genes resistant to Sirolimus therapy were also identfied This series of samples comprises of kidney tissue from (a) 12 week old NZB/W F1 female mice defined as asymptomatic for lupus nephritis (N=4), (b) 36 (N=3) and 42 week (N=3) old NZB/W F1 female mice defined as diseased/symptomatic for lupus nephritis and (c) 36 (N=3)and 42 (N=3) week old NZB/W F1 female mice that are asymptomatic for lupus nephritis on treatment with Sirolimus

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NCAM1: A Novel Autoantigen in Membranous Lupus Nephritis

Project description:Membranous lupus nephritis is a frequent cause of nephrotic syndrome in patients with systemic lupus erythematosus. Unlike phospholipase A2 receptor or thrombospondin type 1 domain containing 7A-associated membranous nephropathy, where known antibodies can be detected within sera by indirect immunofluorescence and/or enzyme-linked immunosorbent assay, it is not possible to monitor disease activity in membranous lupus nephritis where the target autoantigens are mostly unknown. Determination of the target autoantigen has diagnostic significance, informs prognosis, and allows for non-invasive monitoring of disease activity in serum. We utilized mass spectrometry for antigen discovery of laser capture microdissected glomeruli from formalin-fixed paraffin embedded tissue and tissue IgG immunoprecipitation studies from frozen kidney biopsy tissue. We identified neural cell adhesion molecule 1 (NCAM1) to be a target antigen in membranous lupus nephritis and within rare cases of primary membranous nephropathy. The prevalence of NCAM1-associated membranous neuropathy was 5.7% of cases of membranous lupus nephritis. NCAM1 co-localizes with IgG within glomerular immune deposits. Additionally, serum from NCAM1 patients showed reactivity to NCAM1 recombinant protein. The presence of anti-NCAM1 antibodies in sera could allow for non-invasive monitoring of the disease. We propose that NCAM1 is a target autoantigen in a subset of patients with membranous lupus nephritis. Future studies are needed to determine whether anti-NCAM1 antibody levels correlate with disease activity or response to therapy.

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PD-1-PD-L1 Axis Activation Suppresses CD8+ T Cells and Improves Nephritis.

Project description:This SuperSeries is composed of the SubSeries listed below.

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Effect of Sirolimus treatment on lupus nephritis in NZB/W F1 female mice

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Identification of unique microRNA signature associated with lupus nephritis

Project description:MicroRNAs (miRNA) have emerged as an important new class of modulators of gene expression. In this sudy we investigated miRNA that are differentially expressed in lupus nephritis. Microarray technology was used to investigate differentially expressed miRNA in PBMCs and EBV-transformed cell lines obtained from lupus nephritis patients and controls. TaqMan-based stem-loop real-time PCR was used for validation. Microarray analysis of miRNA expressed in African Americans (AA) derived lupus nephritis samples revealed 29 differentially expressed miRNA, of 850 tested. Microarray analysis of miRNA expressed in European American (EA) derived lupus nephritis samples revealed 50 differentially expressed miRNA, of 850 tested.

2011-12-30 | GSE21384 | GEO

PD-1-PD-L1 Axis Activation Suppresses CD8+ T Cells and Improves Nephritis [RNA-seq]

Project description:PD-1-PD-L1 Axis Activation Suppresses CD8+ T Cells and Improves Nephritis [RNA-seq]

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