IL-9-producing invariant NKT cells protect against DSS-induced colitis in an IL-4-dependent manner.
Although the T-helper type 9 (Th9) subset has recently been revisited, interleukin (IL)-9-producing invariant natural killer T (iNKT) cells remain poorly characterized. Moreover, whether IL-9-producing iNKT cells regulate colitis is unknown. Here, we investigated functions of IL-9-producing iNKT cells in dextran sulfate sodium (DSS)-induced colitis. Wild-type (WT) mice attenuated colitis compared to Jα18(-/-) mice, which were restored by the adoptive transfer of WT, but not IL-4-deficient iNKT cells. IL-4-deficient iNKT cells failed to produce IL-9, which was reversed by recombinant IL-4. Furthermore, iNKT cells, pre-incubated with anti-CD3+CD28 monoclonal antibodies and IL-4+tumor growth factor (TGF)-β (IL-9(+) iNKT), suppressed colitis in Jα18(-/-) mice, whereas pre-incubated IL-4-deficient iNKT cells did not. IL-9 blockade reversed IL-9(+) iNKT cell-mediated colitis by increasing colonic IL-17A and interferon (IFN)-γ transcripts, but decreasing IL-9, IL-10, TGF-β, PU.1, IFN regulatory factor 4, and signal transducer and activator of transcription 5 in Jα18(-/-) mice. In conclusion, IL-9-producing iNKT cells protect against DSS-induced colitis through IFN-γ and IL-17A suppression, but IL-10 and TGF-β enhancement, depending on the IL-4 production by iNKT cells.
Department of Pathology and Laboratory of Immune Regulation in Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea.
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Kim
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Chung
D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000276:immunology* / Q000378:metabolism* / Q000517:prevention & control; D016264:Dextran Sulfate / Q000009:adverse effects; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D020381:Interleukin-17 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis* / Q000276:immunology; D016906:Interleukin-9 / Q000096:biosynthesis* / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000096:biosynthesis
D020381:Interleukin-17; D016906:Interleukin-9; D011948:Receptors, Antigen, T-Cell; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma; D016264:Dextran Sulfate