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| Status |
Public on Mar 17, 2024 |
| Title |
In the aftermath of stroke or myocardial infarction, neutrophil extracellular traps disrupt systemic immunoglobulin production |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Post-injury dysfunction of humoral immunity accounts for infections and poor outcome in cardiovascular diseases. Immunoglobulin A (IgA), the most abundant mucosal antibody is produced by plasma B cells in intestinal Peyer’s patches (PP) and lamina propria. Here, we show that stroke and myocardial ischemia (MI) patients had strongly reduced IgA blood levels. This was phenocopied in experimental mouse models where decreased plasma and fecal IgA were accompanied by rapid and macroscopic shrinkage of PP caused by substantial B cell loss. Stroke/MI triggered neutrophils to release neutrophil extracellular traps (NETs). Depletion of neutrophils, NET-degradation, or blockade of NET-release inhibited PP shrinkage and loss of B cells and IgA in stroke mice. Also, stroke and MI patients had higher amounts of circulating NETs, correlating with reduced IgA levels. Strikingly, stroke patients treated with DNase-I had reduced circulating NETs and stable IgA levels. Our results unveil how tissue-injury-triggered systemic NET release disrupts physiological IgA secretion and how this can be inhibited in patients.
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| Overall design |
12 C57BL/6JHsd wild-type male mice were randomly divided into two groups that underwent either sham surgery or ischemic brain injury. Gene expression profiling analysis was performed on data obtained by high-throughput total-RNA sequencing on isolated B cells from the Peyer's Patches of the mice intestines.
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| Contributor(s) |
Tuz AA, Ghosh S, Gallert M, Ttoouli D |
| Citation missing |
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| Submission date |
Jan 28, 2024 |
| Last update date |
Mar 17, 2024 |
| Contact name |
Vikramjeet Singh |
| E-mail(s) |
Vikramjeet.Singh@uk-essen.de
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| Organization name |
University Duisburg-Essen
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| Department |
Institute for Experimental Immunology and Imaging
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| Street address |
Universitätsstr. 2
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| City |
Essen |
| State/province |
Nordrhein-Westfalen |
| ZIP/Postal code |
45141 |
| Country |
Germany |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA1070340 |
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