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Ablation of IL-17A leads to severe colitis in IL-10-deficient mice: implications of myeloid-derived suppressor cells and NO production.
- Source :
-
International immunology [Int Immunol] 2020 Mar 07; Vol. 32 (3), pp. 187-201. - Publication Year :
- 2020
-
Abstract
- 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.<br /> (© The Japanese Society for Immunology. 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
- Subjects :
- Animals
Body Weight
Inflammation immunology
Interleukin-10 deficiency
Interleukin-17 deficiency
Mice
Mice, Inbred C57BL
Mice, Knockout
Nitric Oxide analysis
Nitric Oxide immunology
Nitric Oxide Synthase Type II deficiency
Nitric Oxide Synthase Type II immunology
Colitis immunology
Interleukin-10 immunology
Interleukin-17 immunology
Myeloid-Derived Suppressor Cells immunology
Nitric Oxide biosynthesis
Subjects
Details
- Language :
- English
- ISSN :
- 1460-2377
- Volume :
- 32
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- International immunology
- Publication Type :
- Academic Journal
- Accession number :
- 31755523
- Full Text :
- https://doi.org/10.1093/intimm/dxz076