Interleukin 27 Protects From Gastric Atrophy and Metaplasia During Chronic Autoimmune Gastritis
| Autor: | Christine P. Petersen, Kevin A. Bockerstett, Richard J. DiPaolo, Christine N. Noto, Ryan M. Teague, Lindsey M. Kuehm, Eric L. Ford, Jason C. Mills, James R. Goldenring, Chun Fung Wong |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
CD4-Positive T-Lymphocytes Male Pathology Chronic gastritis Severity of Illness Index Immune Regulation Mice 0302 clinical medicine Metaplasia Parietal cell Original Research Mice Knockout SPEM spasmolytic polypeptide-expressing metaplasia Stomach Gastroenterology CD44v9 CD44 variant 9 Recombinant Proteins medicine.anatomical_structure EpCAM epithelial cell adhesion molecule Gastritis 030211 gastroenterology & hepatology Lymphocyte Female medicine.symptom rIL27 recombinant interleukin 27 Transcription GS-II griffonia simplicifolia medicine.medical_specialty Autoimmune Gastritis PBS phosphate-buffered saline Th helper T cell Autoimmune Diseases Minor Histocompatibility Antigens 03 medical and health sciences cDNA complementary DNA Immune system EBI Epstein-Barr Virus-Induced Gene medicine Gastric mucosa MHC major histocompatibility complex Animals Humans IFN interferon lcsh:RC799-869 Receptors Cytokine Mouse Model Hepatology business.industry Interleukins scRNA single-cell RNA PDX1 pancreatic and duodenal homeobox 1 medicine.disease qRT-PCR quantitative reverse-transcription polymerase chain reaction HDT high-dose tamoxifen IL interleukin Treg regulatory T cells Disease Models Animal 030104 developmental biology APC antigen-presenting cell IF immunofluorescent Gastric Mucosa Chronic Disease lcsh:Diseases of the digestive system. Gastroenterology GIF gastric intrinsic factor Atrophy business Precancerous Conditions |
| Zdroj: | Cellular and Molecular Gastroenterology and Hepatology Cellular and Molecular Gastroenterology and Hepatology, Vol 10, Iss 3, Pp 561-579 (2020) |
| ISSN: | 2352-345X |
| Popis: | 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. Graphical abstract |
| Databáze: | OpenAIRE |
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