The immunological and genetic basis of inflammatory bowel disease

被引:1404
作者
Bouma, G
Strober, W
机构
[1] NIAID, Mucosal Immun Sect, NIH, Clin Invest Lab, Bethesda, MD 20892 USA
[2] Vrije Univ Amsterdam, Med Ctr, Immunogenet Lab, Amsterdam, Netherlands
关键词
D O I
10.1038/nri1132
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The inflammatory bowel diseases (IBDs), Crohn's disease and ulcerative colitis, are chronic inflammatory disorders of the gastrointestinal tract. Enormous progress has been made recently in understanding the pathogenesis of these diseases. Through the study of patients and mouse models, it has emerged that Crohn's disease is driven by the production of interleukin-12 (IL-12) and interferon-gamma (IFN-gamma), whereas ulcerative colitis is probably driven by the production of IL-13. A second area of progress is in the identification of specific genetic abnormalities that are responsible for disease. The most important finding is the identification of mutations in the gene that encodes NOD2 (nucleotide-binding oligomerization domain 2) protein in a subgroup of patients with Crohn's disease. Here, we discuss these recent findings and the implications for therapy.
引用
收藏
页码:521 / 533
页数:13
相关论文
共 140 条
  • [81] Cell contact-dependent immunosuppression by CD4+CD25+ regulatory T cells is mediated by cell surface-bound transforming growth factor β
    Nakamura, K
    Kitani, A
    Strober, W
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 2001, 194 (05) : 629 - 644
  • [82] Regulation of T-cell apoptosis in inflammatory bowel disease: to die or not to die, that is the mucosal question
    Neurath, MF
    Finotto, S
    Fuss, I
    Boirivant, M
    Galle, PR
    Strober, W
    [J]. TRENDS IN IMMUNOLOGY, 2001, 22 (01) : 21 - 26
  • [83] ANTIBODIES TO INTERLEUKIN-12 ABROGATE ESTABLISHED EXPERIMENTAL COLITIS IN MICE
    NEURATH, MF
    FUSS, I
    KELSALL, BL
    STUBER, E
    STROBER, W
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 1995, 182 (05) : 1281 - 1290
  • [84] The transcription factor T-bet regulates mucosal T cell activation in experimental colitis and Crohn's disease
    Neurath, MF
    Weigmann, B
    Finotto, S
    Glickman, J
    Nieuwenhuis, E
    Iijima, H
    Mizoguchi, A
    Mizoguchi, E
    Mudter, J
    Galle, PR
    Bhan, A
    Autschbach, F
    Sullivan, BM
    Szabo, SJ
    Glimcher, LH
    Blumberg, RS
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 2002, 195 (09) : 1129 - 1143
  • [85] Genetic variation and activity of mouse Nod2, a susceptibility gene for Crohn's disease
    Ogura, Y
    Saab, L
    Chen, FF
    Benito, A
    Inohara, N
    Nuñez, G
    [J]. GENOMICS, 2003, 81 (04) : 369 - 377
  • [86] A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease
    Ogura, Y
    Bonen, DK
    Inohara, N
    Nicolae, DL
    Chen, FF
    Ramos, R
    Britton, H
    Moran, T
    Karaliuskas, R
    Duerr, RH
    Achkar, JP
    Brant, SR
    Bayless, TM
    Kirschner, BS
    Hanauer, SB
    Nuñez, G
    Cho, JH
    [J]. NATURE, 2001, 411 (6837) : 603 - 606
  • [87] A NOVEL METHOD IN THE INDUCTION OF RELIABLE EXPERIMENTAL ACUTE AND CHRONIC ULCERATIVE-COLITIS IN MICE
    OKAYASU, I
    HATAKEYAMA, S
    YAMADA, M
    OHKUSA, T
    INAGAKI, Y
    NAKAYA, R
    [J]. GASTROENTEROLOGY, 1990, 98 (03) : 694 - 702
  • [88] Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12
    Oppmann, B
    Lesley, R
    Blom, B
    Timans, JC
    Xu, YM
    Hunte, B
    Vega, F
    Yu, N
    Wang, J
    Singh, K
    Zonin, F
    Vaisberg, E
    Churakova, T
    Liu, MR
    Gorman, D
    Wagner, J
    Zurawski, S
    Liu, YJ
    Abrams, JS
    Moore, KW
    Rennick, D
    de Waal-Malefyt, R
    Hannum, C
    Bazan, JF
    Kastelein, RA
    [J]. IMMUNITY, 2000, 13 (05) : 715 - 725
  • [89] Orholm M, 2000, SCAND J GASTROENTERO, V35, P1075
  • [90] Pagès F, 2001, EUR CYTOKINE NETW, V12, P97