IL-9-producing invariant NKT cells protect against DSS-induced colitis in an IL-4-dependent manner

Mucosal Immunol. 2013 Mar;6(2):347-57. doi: 10.1038/mi.2012.77. Epub 2012 Aug 15.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Colitis / chemically induced
  • Colitis / immunology*
  • Colitis / metabolism*
  • Colitis / prevention & control
  • Dextran Sulfate / adverse effects
  • Interferon-gamma / biosynthesis
  • Interleukin-10 / biosynthesis
  • Interleukin-17 / biosynthesis
  • Interleukin-4 / biosynthesis*
  • Interleukin-4 / immunology
  • Interleukin-9 / biosynthesis*
  • Interleukin-9 / immunology
  • Mice
  • Mice, Knockout
  • Natural Killer T-Cells / immunology*
  • Natural Killer T-Cells / metabolism*
  • Receptors, Antigen, T-Cell / metabolism
  • Transforming Growth Factor beta / biosynthesis


  • Interleukin-17
  • Interleukin-9
  • Receptors, Antigen, T-Cell
  • Transforming Growth Factor beta
  • Interleukin-10
  • Interleukin-4
  • Interferon-gamma
  • Dextran Sulfate