 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Jun 15, 2023 |
| Title |
Inhibition of NETosis via PAD4 could alleviate the inflammation of giant cell myocarditis |
| Organism |
Rattus norvegicus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Giant cell myocarditis (GCM) is a rare, often rapidly progressive and potentially fatal, disease caused by T-cell-mediated cardiac inflammation that typically affects young and middle-aged adults. The detailed inflammatory response remained unknown, especially the formation of multinucleate giant cells.Methods and Results: Rats were treated with myosin heavy-chain-α peptides to generate a GCM model. We performed single-cell RNA sequencing analysis of 15,714 Cd45 + cells extracted from hearts from GCM rat model and normal rats. We identified 24 subclusters including macrophages, neutrophils, T cells and so on. The GCM was characteristic with macrophage cluster 1, neutrophil cluster 3, macrophage cluster 2, neutrophil cluster 1 and Th17 cells. Two specific macrophage clusters involved in the GCM have roles in phagocytosis, and NETosis was found to contribute into the process of GCM. Its receptor, Ccdc25 , expressed in the macrophage cluster 1 and Th17, suggesting that neutrophils could regulate other immune cells in GCM. Importantly, inhibitor of NETosis, GSK484, could alleviate the inflammation of GCM in vivo. Finally, MPO (a marker of neutrophils) and H3cit (a marker of NETosis) were expressed at higher levels in GCM patients than in DCM patients and healthy controls and neutrophils were part of multinucleated giant cells. IMC analysis revealed that the formation of multinucleate giant cells of GCM.Conclusions: We herein present a comprehensive single-cell landscape of the cardiac immune cells in GCM. In addition, we elucidated the contribution of NETosis to the pathogenesis of GCM, which may serve as a potential therapeutic target in the clinic.
|
| |
|
| Overall design |
Rats were treated with myosin heavy-chain-α peptides to generate a GCM model compare a normal rat model
|
| Web link |
https://pubmed.ncbi.nlm.nih.gov/37534129/
|
| |
|
| Contributor(s) |
Hu Z, Hua X, Mo X, Chang Y, Chen X, Xu Z, Tao M, Hu G, Song J |
| Citation(s) |
37534129 |
| |
| Submission date |
Dec 15, 2022 |
| Last update date |
Sep 18, 2023 |
| Contact name |
Xiuxue Mo |
| E-mail(s) |
molavande@mail.nankai.edu.cn
|
| Organization name |
Nankai University
|
| Street address |
Weijin Road 94, Nankai District
|
| City |
Tianjin |
| ZIP/Postal code |
300071 |
| Country |
China |
| |
|
| Platforms (1) |
| GPL20084 |
Illumina NextSeq 500 (Rattus norvegicus) |
|
| Samples (2) |
|
| Relations |
| BioProject |
PRJNA912772 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE221111_GCM_Seurat3.rds.gz |
165.2 Mb |
(ftp)(http) |
RDS |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
|
|
|
|
 |
