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

Publisher: [Oxford University Press Country of Publication: England NLM ID: 8916182 Publication Model: Print Cited Medium: Internet ISSN: 1460-2377 (Electronic) Linking ISSN: 09538178 NLM ISO Abbreviation: Int Immunol Subsets: MEDLINE

Original Publication: Oxford : [Oxford University Press, 1989-

Colitis/*immunology ; Interleukin-10/*immunology ; Interleukin-17/*immunology ; Myeloid-Derived Suppressor Cells/*immunology ; Nitric Oxide/*biosynthesis; 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

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.
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Keywords: IL-17A; MDSC; colitis; nitric oxide

0 (IL10 protein, mouse)
0 (Il17a protein, mouse)
0 (Interleukin-17)
130068-27-8 (Interleukin-10)
31C4KY9ESH (Nitric Oxide)
EC 1.14.13.39 (Nitric Oxide Synthase Type II)
EC 1.14.13.39 (Nos2 protein, mouse)

Date Created: 20191123 Date Completed: 20201001 Latest Revision: 20201001

20250114

PMC7067553

10.1093/intimm/dxz076

31755523