Oxazolone colitis, a Th2 colitis model resembling ulcerative colitis, is mediated by IL-13-producing NK-T cells

被引:530
作者
Heller, F
Fuss, IJ
Nieuwenhuis, EE
Blumberg, RS
Strober, W
机构
[1] NIAID, Mucosal Immun Sect, Clin Invest Lab, NIH, Bethesda, MD 20892 USA
[2] Harvard Univ, Sch Med, Div Gastroenterol, Brigham & Womens Hosp, Boston, MA 02115 USA
[3] Royal Netherland Acad Arts & Sci, Ter Meulen Fund, Amsterdam, Netherlands
关键词
D O I
10.1016/S1074-7613(02)00453-3
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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 a-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.
引用
收藏
页码:629 / 638
页数:10
相关论文
共 50 条
[1]   ISOLATION AND CHARACTERIZATION OF A CDNA AND GENE CODING FOR A 4TH CD1 MOLECULE [J].
BALK, SP ;
BLEICHER, PA ;
TERHORST, C .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1989, 86 (01) :252-256
[2]   POSITIVE SELECTION OF MOUSE NK1(+) T-CELLS BY CD1-EXPRESSING CORTICAL THYMOCYTES [J].
BENDELAC, A .
JOURNAL OF EXPERIMENTAL MEDICINE, 1995, 182 (06) :2091-2096
[3]   EXPRESSION OF MURINE CD1 ON GASTROINTESTINAL EPITHELIUM [J].
BLEICHER, PA ;
BALK, SP ;
HAGEN, SJ ;
BLUMBERG, RS ;
FLOTTE, TJ ;
TERHORST, C .
SCIENCE, 1990, 250 (4981) :679-682
[4]  
BLUMBERG RS, 1991, J IMMUNOL, V147, P2518
[5]   Oxazolone colitis: A murine model of T helper cell type 2 colitis treatable with antibodies to interleukin 4 [J].
Boirivant, M ;
Fuss, IJ ;
Chu, A ;
Strober, W .
JOURNAL OF EXPERIMENTAL MEDICINE, 1998, 188 (10) :1929-1939
[6]  
BROWN AJ, 1997, CHARACTERIZATION POR, V4, P1
[7]   Interleukins 4 and 13 increase intestinal epithelial permeability by a phosphatidylinositol 3-kinase pathway - Lack of evidence for STAT 6 involvement [J].
Ceponis, PJM ;
Botelho, F ;
Richards, CD ;
McKay, DM .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (37) :29132-29137
[8]  
Chen HJ, 1997, J IMMUNOL, V159, P2240
[9]   Requirement for V(alpha)14 NKT cells in IL-12-mediated rejection of tumors [J].
Cui, JQ ;
Shin, T ;
Kawano, T ;
Sato, H ;
Kondo, E ;
Toura, I ;
Kaneko, Y ;
Koseki, H ;
Kanno, M ;
Taniguchi, M .
SCIENCE, 1997, 278 (5343) :1623-1626
[10]  
Donaldson DD, 1998, J IMMUNOL, V161, P2317