Interleukin 27 Protects From Gastric Atrophy and Metaplasia During Chronic Autoimmune GastritisSummary

Cellular and Molecular Gastroenterology and Hepatology

Chun Fung Wong¹  Christine N. Noto¹  Lindsey M. Kuehm¹  Ryan M. Teague¹  Eric L. Ford¹  Richard J. DiPaolo¹  Kevin A. Bockerstett¹  Jason C. Mills²  James R. Goldenring³  Christine P. Petersen³ 

[1] Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, Saint Louis, Missouri;Division of Gastroenterology, Department of Medicine, Pathology and Immunology, Department of Developmental Biology, Washington University School of Medicine, Saint Louis, Missouri;Nashville Veterans Affairs Medical Center, Department of Surgery, Department of Cell and Developmental Biology, Epithelial Biology Center, Vanderbilt University School of Medicine, Nashville, Tennessee;

关键词: Mouse Model;    Immune Regulation;    Lymphocyte;    Transcription;   

DOI  :  

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown