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Glucocorticoids target the CXCL9/10-CXCR3 axis and confer protection against immune-mediated kidney injury

ABSTRACT: Glucocorticoids target the CXCL9/10-CXCR3 axis and confer protection against immune-mediated kidney injury

PROVIDER: PRJNA899146 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR22225144_1.fastq.gz	Fastqsanger.gz
	SRR22225144_2.fastq.gz	Fastqsanger.gz
	SRR22225145_1.fastq.gz	Fastqsanger.gz
	SRR22225145_2.fastq.gz	Fastqsanger.gz
	SRR22225146_1.fastq.gz	Fastqsanger.gz

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Glucocorticoids target the CXCL9/CXCL10-CXCR3 axis and confer protection against immune-mediated kidney injury.

Project description:Glucocorticoids remain a cornerstone of therapeutic regimes for autoimmune and chronic inflammatory diseases - for example, in different forms of crescentic glomerulonephritis - because of their rapid antiinflammatory effects, low cost, and wide availability. Despite their routine use for decades, the underlying cellular mechanisms by which steroids exert their therapeutic effects need to be fully elucidated. Here, we demonstrate that high-dose steroid treatment rapidly reduced the number of proinflammatory CXCR3+CD4+ T cells in the kidney by combining high-dimensional single-cell and morphological analyses of kidney biopsies from patients with antineutrophil cytoplasmic antibody-associated (ANCA-associated) crescentic glomerulonephritis. Using an experimental model of crescentic glomerulonephritis, we show that the steroid-induced decrease in renal CD4+ T cells is a consequence of reduced T cell recruitment, which is associated with an ameliorated disease course. Mechanistic in vivo and in vitro studies revealed that steroids act directly on renal tissue cells, such as tubular epithelial cells, but not on T cells, which resulted in an abolished renal expression of CXCL9 and CXCL10 as well as in the prevention of CXCR3+CD4+ T cell recruitment to the inflamed kidneys. Thus, we identified the CXCL9/CXCL10-CXCR3 axis as a previously unrecognized cellular and molecular target of glucocorticoids providing protection from immune-mediated pathology.

| S-EPMC9870076 | biostudies-literature

Glucocorticoids target the CXCL9/10-CXCR3 axis and confer protection against immune-mediated kidney injury

Project description:Single-cell RNA-seq of renal T cells from steroid treated or not treated crescentic glomerulonephritis mouse model and steroid treated ANCA-GN patients.

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LSD1 Inhibition eliminates HNSCC coordinated by activated Dendritic Cells, IFNg-CXCL9-CXCR3 and MHC-I

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Macrophage-specific Act1 Knockdown Promoted Adenoma-Adenocarcinoma Transition in Apcmin+/- Mice via Activation of the CXCL9/10-CXCR3 axis

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