Oxazolone colitis, a Th2 colitis model resembling ulcerative colitis, is mediated by IL-13-producing NK-T cells.
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-13Ralpha2-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 alpha-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.
Heller
Frank
F
Mucosal Immunity Section, Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Fuss
Ivan J
IJ
Nieuwenhuis
Edward E
EE
Blumberg
Richard S
RS
Strober
Warren
W
D000276:Adjuvants, Immunologic; D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000276:immunology*; D003093:Colitis, Ulcerative / Q000209:etiology* / Q000276:immunology; D004195:Disease Models, Animal; D006801:Humans; D018793:Interleukin-13 / Q000096:biosynthesis / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010081:Oxazolone; D018418:Th2 Cells / Q000276:immunology*
D000276:Adjuvants, Immunologic; D018793:Interleukin-13; D010081:Oxazolone