Academic Journal
Ablation of IL-17A leads to severe colitis in IL-10-deficient mice: implications of myeloid-derived suppressor cells and NO production
| العنوان: | Ablation of IL-17A leads to severe colitis in IL-10-deficient mice: implications of myeloid-derived suppressor cells and NO production |
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| المؤلفون: | Tachibana, Masashi, Watanabe, Nobumasa, Koda, Yuzo, Oya, Yukako, Kaminuma, Osamu, Katayama, Kazufumi, Fan, Zifei, Sakurai, Fuminori, Kawabata, Kenji, Hiroi, Takachika, Mizuguchi, Hiroyuki |
| المساهمون: | Osaka University Graduate School of Medicine, Tokyo Biochemical Research Foundation, Genomics for Agricultural Innovation, Ministry of Agriculture, Forestry and Fisheries, Platform Project for Supporting Drug Discovery and Life Science Research, Japan Agency for Medical Research and Development |
| المصدر: | International Immunology ; volume 32, issue 3, page 187-201 ; ISSN 1460-2377 |
| بيانات النشر: | Oxford University Press (OUP) |
| سنة النشر: | 2019 |
| الوصف: | IL-10 is an immune regulatory cytokine and its genetic defect leads to gastrointestinal inflammation in humans and mice. Moreover, the IL-23/Th17 axis is known to be involved in these inflammatory disorders. IL-17A, a representative cytokine produced by Th17 cells, has an important role for the pathological process of inflammatory diseases. However, the precise function of IL-17A in inflammatory bowel disease (IBD) remains controversial. In this study, we evaluated the effect of IL-17A on colitis in IL-10-deficient (Il10−/−) mice. Mice lacking both IL-10 and IL-17A (Il10−/−Il17a−/−) suffered from fatal wasting and manifested more severe colitis compared with Il10−/−Il17a+/− mice. Moreover, we found that CD11b+Gr-1+ myeloid-derived suppressor cells (MDSCs) accumulated in the bone marrow, spleen and peripheral blood of Il10−/−Il17a−/− mice. These MDSCs highly expressed inducible nitric oxide synthase (iNOS) (Nos2) and suppressed the T-cell response in vitro in a NOS-dependent manner. In correlation with these effects, the concentration of nitric oxide was elevated in the serum of Il10−/−Il17a−/− mice. Surprisingly, the severe colitis observed in Il10−/−Il17a−/− mice was ameliorated in Il10−/−Il17a−/−Nos2−/− mice. Our findings suggest that IL-17A plays suppressive roles against spontaneous colitis in Il10−/− mice in an iNOS-dependent manner and inhibits MDSC differentiation and/or proliferation. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1093/intimm/dxz076 |
| DOI: | 10.1093/intimm/dxz076/31616016/dxz076.pdf |
| الاتاحة: | http://dx.doi.org/10.1093/intimm/dxz076 http://academic.oup.com/intimm/advance-article-pdf/doi/10.1093/intimm/dxz076/31616016/dxz076.pdf https://academic.oup.com/intimm/article/32/3/187/5637709 |
| Rights: | https://creativecommons.org/licenses/by-nc/4.0/ |
| رقم الانضمام: | edsbas.DB91BE4A |
| قاعدة البيانات: | BASE |
| DOI: | 10.1093/intimm/dxz076 |
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