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| Status |
Public on Feb 17, 2026 |
| Title |
Splenic nerves NE-β2AR axis exacerbate septic acute kidney injury via modulating neutrophilic immunosuppression [scRNA-seq] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Sepsis is characterized by chronic inflammation and immunosuppression, two immune states that hinder effective infection control and significantly contribute to renal pathological damage. Recent studies have underscored the crucial role of splenic neuroimmune interactions in immune response regulation. However, the precise mechanisms and functions of splenic nerve regulation of splenic immune responses in sepsis-associated acute kidney injury (SA-AKI) remain obscure. Our research suggests that preemptive Splenic Denervation in mice can mitigate sepsis-induced renal injury, while local norepinephrine injection into the spleen exacerbates sepsis-induced kidney damage in the cecal ligation and puncture (CLP) mouse model. Targeted blockade of splenic β2-adrenergic receptor signaling leads to increased survival rates and diminished renal damage in the mice treated with CLP. Subsequent experiments involving local splenic administration of Gr-1 antibodies and myeloid cell-specific conditional knockout of Adrb2 in mice validate that during sepsis, NE/β2-AR signaling can impact splenic neutrophils, fostering the progression of acute sepsis. Mechanistic inquiries reveal that splenic Adrb2 signaling boosts neutrophil PGE2 signaling through the cAMP pathway, promoting Th1 activation, diminishing local bacterial infections, and ameliorating SA-AKI. Furthermore, Blocking ADRB2 or PGE2 synthesizing signal significantly modulates the immunosuppression effect of neutrophils, promoting anti-bacterial Th1 immune response. These studies elucidate the role of splenic NE-ADRB2 signaling in regulating neutrophil immunosuppressive functions, thereby influencing the advancement of sepsis and renal tissue damage.
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| Overall design |
For cecal ligation and puncture (CLP)-induced AKI model, mice were anesthetized with 2% isoflurane, then the cecum was ligated at 50% or 30% length and punctured through with a 22-gauge needle. Spleen cells from CLP mice were harvested for single-cell RNA sequencing
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| Citation missing |
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| BioProject |
PRJNA1224852 |
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| Submission date |
Feb 18, 2025 |
| Last update date |
Feb 17, 2026 |
| Contact name |
Xiaoqian Hu |
| E-mail(s) |
hux022325@gmail.com
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| Organization name |
Fudan University
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| Street address |
No. 130, Dongan Road, Xuhui District, Shanghai
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| City |
Shanghai |
| ZIP/Postal code |
200000 |
| Country |
China |
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| Platforms (1) |
| GPL9185 |
Illumina Genome Analyzer (Mus musculus) |
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| Samples (1) |
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| Supplementary file |
Size |
Download |
File type/resource |
| GSE289831_RAW.tar |
106.7 Mb |
(http)(custom) |
TAR (of MTX, TSV) |
SRA Run Selector |
| Raw data are available in SRA |
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