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Kidney VISTA prevents IFNγ-IL-9 axis-mediated tubulointerstitial fibrosis after acute glomerular injury

ABSTRACT: Kidney VISTA prevents IFNγ-IL-9 axis-mediated tubulointerstitial fibrosis after acute glomerular injury

PROVIDER: PRJNA750914 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR15305021_1.fastq.gz	Fastqsanger.gz
	SRR15305021_2.fastq.gz	Fastqsanger.gz
	SRR15305022_1.fastq.gz	Fastqsanger.gz
	SRR15305022_2.fastq.gz	Fastqsanger.gz

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Similar Datasets

Kidney VISTA prevents IFNγ-IL-9 axis-mediated tubulointerstitial fibrosis after acute glomerular injury

Project description:Backgrounds: The present study addressed whether V-domain Ig suppressor of T cell activation (VISTA), constitutively expressed in kidney macrophages, has a protective role in tubulointerstitial fibrotic transformation after acute antibody-mediated glomerulonephritis. Methods: Wild-type (WT) and VISTA-deficient (Vsir-/-, KO) mice were treated with nephrotoxic serum to induced acute antibody-mediated glomerulonephritis, and their cytokine and fibrosis profiles were compared. Results: VISTA was highly expressed in kidney macrophages (resident more than infiltrating subset). If VISTA was depleted, tubules suffered further damage after glomerular injury. In damaged Vsir–/– mice, the contact frequency of macrophages with infiltrated T cells increased, and then the immunometabolic characteristics of T cells changed to overproduction of interferon-γ. The Vsir–/– parenchymal tissue cells responded to this altered milieu as more producing interleukin-9, which augmented tubulointerstitial fibrosis and irreversible kidney dysfunction. The blocking antibodies against interferon-γ and interleukin-9 protected above pathological process by VISTA depletion. Conclusions: VISTA is a sentinel protein of kidney macrophages, which prevents tubulointerstitial fibrosis via interferon-γ-interleukin-9 axis after acute antibody-mediated glomerular injury.

2021-08-04 | GSE181163 | GEO

Kidney VISTA prevents IFN-γ/IL-9 axis-mediated tubulointerstitial fibrosis after acute glomerular injury.

Project description:Severe glomerular injury ultimately leads to tubulointerstitial fibrosis that determines patient outcome, but the immunological molecules connecting these processes remain undetermined. The present study addressed whether V-domain Ig suppressor of T cell activation (VISTA), constitutively expressed in kidney macrophages, plays a protective role in tubulointerstitial fibrotic transformation after acute antibody-mediated glomerulonephritis. After acute glomerular injury using nephrotoxic serum, tubules in the VISTA-deficient (Vsir-/-) kidney suffered more damage than those in WT kidneys. When interstitial immune cells were examined, the contact frequency of macrophages with infiltrated T cells increased and the immunometabolic features of T cells changed to showing high oxidative phosphorylation and fatty acid metabolism and overproduction of IFN-γ. The Vsir-/- parenchymal tissue cells responded to this altered milieu of interstitial immune cells as more IL-9 was produced, which augmented tubulointerstitial fibrosis. Blocking antibodies against IFN-γ and IL-9 protected the above pathological process in VISTA-depleted conditions. In human samples with acute glomerular injury (e.g., antineutrophil cytoplasmic autoantibody vasculitis), high VISTA expression in tubulointerstitial immune cells was associated with low tubulointerstitial fibrosis and good prognosis. Therefore, VISTA is a sentinel protein expressed in kidney macrophages that prevents tubulointerstitial fibrosis via the IFN-γ/IL-9 axis after acute antibody-mediated glomerular injury.

| S-EPMC8718152 | biostudies-literature

Human kidney proteomics, glomerular and tubular cellular and matrix fractions

Project description:Glomerular and tubulointerstitial fractions were enriched from human kidneys samples. Ages of human kidney samples: 15, 29, 37, 61, 67 and 69 years of age. The glomerular and tubulointerstitial samples were processed to enrich for extracellular matrix components and the fractions analysed by mass spectrometry.

2022-02-22 | PXD022219 | Pride

RNA of murine macrophages and neutrophils treated with LPS and VISTA

Project description:V-domain immunoglobulin suppressor of T-cell activation (VISTA) has emerged as a unique immunoregulatory receptor on cells of the myeloid lineage. Agonizing VISTA on myeloid cells has recently been demonstrated to have a profound effect on dampening inflammatory responses. VISTA has been proposed to function both as a ligand and as a receptor, yet the role of VISTA as a ligand has been largely ignored. In this experiment, macrophages and neutrophils were isolated from mice and treated with LPS and VISTA to examine the effect of VISTA in dampening acute inflammation.

2022-12-02 | E-MTAB-10856 | biostudies-arrayexpress

Shared molecular targets in the glomerular transcriptome from patients with nephrotic syndrome and ANCA-associated vasculitis

Project description:Glomerular transcriptome from human kidney biopsies in Neptune and ERCB. A subset of samples profiled in this analysis were also profiled in Series GSE68127, and in GSE104066. Corresponding tubulointerstitial transcriptome data is submitted under GEO ID: GSE108113. RNA from the glomerular compartment was extracted and processed for hybridization on Affymetrix ST 2.1 microarrays, annotated using Human Entrez Gene ID custom CDF version 19. This dataset is part of the TransQST collection.

2018-05-17 | E-GEOD-108109 | biostudies-arrayexpress

Human kidney proteomics, glomerular and tubular cellular and matrix fractions

Project description:kidney samples: 15, 29, 37, 61, 67 and 69 years of age. The glomerular and tubulointerstitial samples were processed to enrich for extracellular matrix components and the fractions analysed by mass spectrometry.

2021-10-13 | PXD026002 | Pride

VISTA re-programs macrophage biology through the combined regulation of tolerance and anti-inflammatory pathways

Project description:1) BMDMs treated with anti-VISTA under tolerizing and immunizing conditions. 2) Time course analysis of anti-VISTA-induced alterations in human monocytes after anti-VISTA treatment. 3) Time course analysis of anti-VISTA-induced alterations in BMDMs after anti-VISTA treatment. 4) Single cell ATAC-seq of BMDMs tolerized in the presence or IgG or anti-VISTA.

2020-09-05 | GSE157518 | GEO

Shared molecular targets in the glomerular transcriptome from patients with nephrotic syndrome and ANCA-associated vasculitis

2018-05-17 | GSE108109 | GEO

VISTA is an activating receptor that binds the proteoglycan Syndecan-2 on monocytes.

Project description:As indicated by its name, V-domain Ig suppressor of T cell activation (VISTA) is thought to primarily serve as an inhibitory protein that limits immune responses. VISTA-antibodies can dampen the effects of several concomitantly elicited activation signals including T cell receptor (TCR) and Toll-like receptor (TLR) activation, but it is currently unclear if VISTA agonism could singly affect immune cell biology. In this study, we discovered two novel agonistic VISTA antibodies and characterized their effects on human peripheral blood mononuclear cells (PBMC) by scRNA/CITE-seq. Both antibodies agonize VISTA in an Fc-functional manner to elicit transcriptional and functional changes in monocytes consistent with activation. We also used pentameric VISTA to identify Syndecan-2 (Sdc2) and several heparan sulfate proteoglycan (HSPG) synthesis genes as novel regulators of VISTA binding to monocytic cells adding further evidence of bidirectional signaling. Together, our study highlights several novel aspects of VISTA biology that have yet to be uncovered in myeloid cells and serves as a foundation for future research.

2021-05-04 | GSE173747 | GEO

Shared molecular targets in the glomerular and tubulointerstitial transcriptomes from patients with nephrotic syndrome and ANCA-associated vasculitis

Project description:Shared molecular targets in the glomerular and tubulointerstitial transcriptomes from patients with nephrotic syndrome and ANCA-associated vasculitis

| PRJNA422466 | ENA

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