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Series GSE234742 Query DataSets for GSE234742
Status Public on May 16, 2024
Title The Protective Role of Integrin α4β7 and Amphiregulin-Expressing Innate Lymphoid Cells in Lupus Nephritis
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Type-2 innate lymphoid cells (ILC2s) have emerged as key immune-response regulators in renal-inflammatory diseases such as lupus nephritis. However, the adhesion and migration of ILC2s, including in the homeostatic and diseased kidney, are poorly understood. By integrating transcriptomic profiling, flow cytometry, live-cell imaging, and in-vivo models, we showed that renal ILCs are retained in the homeostatic kidney by the adherence of their cell-surface integrin α4β7 to VCAM-1, E-cadherin or fibronectin on structural kidney cells. When cultured on these ligands, ILC2s demonstrated remarkable migration. Knocking down integrin-α4β7 expression reduced ILC2 Areg production. In lupus nephritis, TLR7/9 may downregulate ILC2 expression of integrin-α4β7, thereby both reducing Areg expression and promoting ILC2 egress. Areg loss may promote the proinflammatory-cytokine secretion by T cells. IL-33 upregulated ILC2 integrin-α4β7 and Areg expression. Notably, IL-33 treatment enhanced survival in lupus nephritis by mitigating kidney inflammation. Thus, ILC2 adhesion may be a therapeutic target for autoimmune kidney diseases.
 
Overall design To investigate the role of ILCs in lupus nephritis, we used pooledkidneys from old or young MRL-lpr mice. Renal immune cells, particularly innate lymphoid cells, were further enriched using density-gradient centrifugation and an ILC enrichment kit to ensure that the scRNA-seq analysis detected a low frequency cell population of ILCs in the oldMRL-lpr kidney.
 
Contributor(s) Ryu S, Kim HY
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Submission date Jun 12, 2023
Last update date May 17, 2024
Contact name Hye Young Kim
Organization name Seoul National University
Street address 103 Daehak-ro, Jongro-gu
City Seoul
ZIP/Postal code 03080
Country South Korea
 
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (2)
GSM7474180 Old MRL-lpr kidney
GSM7474181 Young MRL-lpr kidney
Relations
BioProject PRJNA982838

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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE234742_RAW.tar 236.2 Mb (http)(custom) TAR (of MTX, TSV)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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