Oxazolone Colitis, a Th2 Colitis Model Resembling Ulcerative Colitis, Is Mediated by IL-13-Producing NK-T Cells

• Published in: Immunity (Cambridge, Mass.) Mass.), 2002-11, Vol.17 (5), p.629-638
• Main Authors: Heller, Frank, Fuss, Ivan J, Nieuwenhuis, Edward E, Blumberg, Richard S, Strober, Warren
• Format: Article
• Language: English
• Subjects: Adjuvants, Immunologic; Animals; Cloning; Colitis - chemically induced; Colitis - immunology; Colitis, Ulcerative - etiology; Colitis, Ulcerative - immunology; Cytokines; Disease; Disease Models, Animal; Humans; Immune system; Inflammatory bowel disease; Interleukin-13 - biosynthesis; Interleukin-13 - immunology; Killer Cells, Natural - immunology; Lymphocytes; Male; Mice; Mice, Inbred C57BL; Oxazolone; T cell receptors; Th2 Cells - immunology
• ISSN: 1074-7613; 1097-4180
• DOI: 10.1016/S1074-7613(02)00453-3

Oxazolone colitis (OC) is an experimental colitis that has a histologic resemblance to human ulcerative colitis. Here we show that IL-13 production is a significant pathologic factor in OC since its neutralization by IL-13Rα2-Fc administration prevents colitis. We further show that OC is mediated by NK-T cells since it can be induced neither in mice depleted of NK-T cells nor in mice that cannot present antigen to NK-T cells and mice lacking an NK-T cell-associated TCR. Finally, we show that NK-T cells are the source of the IL-13, since they produce IL-13 upon stimulation by α-galactosylceramide, an NK-T cell-specific antigen. These data thus describe a cellular mechanism underlying an experimental colitis that may explain the pathogenesis of ulcerative colitis.