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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
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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.
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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.
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Contributor(s) |
Ryu S, Kim HY |
Citation missing |
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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
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Street address |
103 Daehak-ro, Jongro-gu
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City |
Seoul |
ZIP/Postal code |
03080 |
Country |
South Korea |
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Platforms (1) |
GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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Samples (2) |
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Relations |
BioProject |
PRJNA982838 |
Supplementary file |
Size |
Download |
File type/resource |
GSE234742_RAW.tar |
236.2 Mb |
(http)(custom) |
TAR (of MTX, TSV) |
SRA Run Selector |
Raw data are available in SRA |
Processed data provided as supplementary file |
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