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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Oct 01, 2024 |
| Title |
Interleukin 27 Protects From Gastric Atrophy and Metaplasia During Chronic Autoimmune Gastritis |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Background & Aims: The association between chronic inflammation and gastric carcinogenesis is well established, but it is not clear how immune cells and cytokines regulate this process. We investigated the role of interleukin 27 (IL27) in the development of gastric atrophy, hyperplasia, and metaplasia (preneoplastic lesions associated with inflammation-induced gastric cancer) in mice with autoimmune gastritis. Methods: We performed studies with TxA23 mice (control mice), which express a T-cell receptor against the H+/K+ adenosine triphosphatase α chain and develop autoimmune gastritis, and TxA23xEbi3-/- mice, which develop gastritis but do not express IL27. In some experiments, mice were given high-dose tamoxifen to induce parietal cell atrophy and spasmolytic polypeptide-expressing metaplasia (SPEM). Recombinant IL27 was administered to mice with mini osmotic pumps. Stomachs were collected and analyzed by histopathology and immunofluorescence; we used flow cytometry to measure IL27 and identify immune cells that secrete IL27 in the gastric mucosa. Single-cell RNA sequencing was performed on immune cells that infiltrated stomach tissues. Results: We identified IL27-secreting macrophages and dendritic cell in the corpus of mice with chronic gastritis (TxA23 mice). Mice deficient in IL27 developed more severe gastritis, atrophy, and SPEM than control mice. Administration of recombinant IL27 significantly reduced the severity of inflammation, atrophy, and SPEM in mice with gastritis. Single-cell RNA sequencing showed that IL27 acted almost exclusively on stomach-infiltrating CD4+ T cells to suppress expression of inflammatory genes. Conclusions: In studies of mice with autoimmune gastritis, we found that IL27 is an inhibitor of gastritis and SPEM, suppressing CD4+ T-cell–mediated inflammation in the gastric mucosa.
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| Overall design |
800 ng of carrier-free rIL27 (2799-ML-010/CF; R&D Systems, Minneapolis, MN) in 200 uL of sterile PBS was loaded into mini osmotic pumps (model 2004; Alzet, Cupertino, CA) based on published effective doses in mice. Pumps were implanted subcutaneously into control TxA23 mice at 3 months of age. Mice were euthanized 4 weeks after implantation. Pumps containing only sterile PBS were used as sham controls. For scRNA sequencing analysis, CD45+ propidium iodide cells- were sorted from the gastric mucosa to separate live immune cells from dead and epithelial cells. These cell suspensions then were washed once and loaded onto the 10X Genomics Chromium Controller using the 5' v1.1 protocol following manufacturer's recommendations.
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| Contributor(s) |
Bockerstett KA, DiPaolo RJ |
| Citation(s) |
32376420 |
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| Submission date |
Oct 01, 2024 |
| Last update date |
Oct 03, 2024 |
| Contact name |
Richard DiPaolo |
| E-mail(s) |
richard.dipaolo@health.slu.edu
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| Organization name |
Saint Louis Univeristy
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| Street address |
1100 S Grand Ave
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| City |
St. Louis |
| State/province |
MO |
| ZIP/Postal code |
63104 |
| Country |
USA |
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| Platforms (1) |
| GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
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| Samples (2) |
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| Relations |
| BioProject |
PRJNA1167764 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE278552_RAW.tar |
173.7 Mb |
(http)(custom) |
TAR (of MTX, TSV) |
SRA Run Selector |
| Raw data are available in SRA |
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