期刊
JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY
卷 28, 期 6, 页码 982-991出版社
WILEY-BLACKWELL
DOI: 10.1111/jgh.12144
关键词
autoimmune gastritis; autoantibody production; cytokine
资金
- Japanese Government
- Astellas Pharma Inc.
- Japan Society for the Promotion of Science (JSPS) [20390207, 21229009, 23590973]
- Ministry of Health, Labour and Welfare, Japan
- Japanese Society of Gastroenterology
- Kato Memorial Trust for Nambyo Research
- Waksman Foundation of Japan
- Grants-in-Aid for Scientific Research [20390207, 23590973] Funding Source: KAKEN
Background and Aim Autoimmune gastritis (AIG), an organ-specific autoimmune disease, is accompanied by achlorhydria, pernicious anemia, gastric carcinoid tumors, and gastric cancer. Patients with AIG initially respond to corticosteroids but have a great potential to relapse after treatment is withdrawn. This study examines the roles of cytokines in order to identify potential therapeutic options for AIG patients. Methods Using a mouse model of AIG, we monitored disease progression and administered antibodies in vivo to block cytokines. Results We developed a mouse model of AIG with early onset and rapid progression in which neonatal thymectomy (NTx) was performed on programmed cell death 1-deficient (PD-1/) mice on the BALB/c background. Using NTxPD-1/ mice, we found that in AIG lesions, interferon-, and tumor necrosis factor (TNF)- together with interleukin-21 (IL-21) were highly expressed in the inflamed gastric mucosa. In addition, as with the injection of dexamethasone, in vivo administration of either anti-TNF- or anti-IL-21 suppressed the development of AIG in NTxPD-1/ mice. Conclusions These data reveal the essential role of IL-21 in the development of AIG and suggest that in addition to corticosteroids, anti-TNF- as well as anti-IL-21 have the potential to induce the remission of AIG, offering additional therapeutic options for AIG patients.
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