論文

査読有り 国際誌
2020年3月7日

Ablation of IL-17A leads to severe colitis in IL-10-deficient mice: implications of myeloid-derived suppressor cells and NO production.

International immunology
  • Masashi Tachibana
  • ,
  • Nobumasa Watanabe
  • ,
  • Yuzo Koda
  • ,
  • Yukako Oya
  • ,
  • Osamu Kaminuma
  • ,
  • Kazufumi Katayama
  • ,
  • Zifei Fan
  • ,
  • Fuminori Sakurai
  • ,
  • Kenji Kawabata
  • ,
  • Takachika Hiroi
  • ,
  • Hiroyuki Mizuguchi

32
3
開始ページ
187
終了ページ
201
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1093/intimm/dxz076

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.

リンク情報
DOI
https://doi.org/10.1093/intimm/dxz076
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/31755523
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7067553

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