Unravelling the pathogenesis of inflammatory bowel disease

Nature

Volumn 448, Issue 7152, 2007, Pages 427-434

  Xavier, R J ^a,b   Podolsky, D K ^a  

^a HARVARD MEDICAL SCHOOL   (United States)

^b MASSACHUSETTS GENERAL HOSPITAL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BACTERIUM; COMMENSAL; DIGESTIVE SYSTEM DISORDER; DISEASE; ENVIRONMENTAL FACTOR; GENE; IMMUNITY; PATHOGEN;

ADAPTIVE IMMUNITY; AUTOPHAGY; COMMENSAL; DISEASE PREDISPOSITION; ENTERITIS; ENVIRONMENTAL FACTOR; EPITHELIUM; GENETIC SUSCEPTIBILITY; HOMEOSTASIS; IMMUNE DYSREGULATION; IMMUNOPATHOLOGY; INNATE IMMUNITY; MICROORGANISM; MUCOSA; NONHUMAN; PRIORITY JOURNAL; REVIEW; ULCERATIVE COLITIS;

ANIMALS; AUTOPHAGY; COLITIS; GENETIC PREDISPOSITION TO DISEASE; HUMANS; IMMUNITY, NATURAL; INFLAMMATORY BOWEL DISEASES; INTESTINAL MUCOSA;

MURINAE;

EID: 34547176642     PISSN: 00280836     EISSN: 14764679     Source Type: Journal    
DOI: 10.1038/nature06005     Document Type: Review

References (98)

1. Podolsky, D. K. Inflammatory bowel disease. N. Engl. J. Med. 347, 417-429 (2002).
2. Orholm, M. et al. Familial occurrence of inflammatory bowel disease. N. Engl. J. Med. 324, 84-88 (1991).
3. Tysk, C., Lindberg, E., Jarnerot, G. & Floderus-Myrhed, B. Ulcerative colitis and Crohn's disease in an unselected population of monozygotic and dizygotic twins. A study of heritability and the influence of smoking. Gut 29, 990-996 (1988).
4. Hugot, J. P. et al. Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease. Nature 411, 599-603 (2001).
5. Ogura, Y. et al. A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease. Nature 411, 603-606 (2001).
6. Duerr, R. H. et al. A genome-wide association study identifies IL23R as an inflammatory bowel disease gene. Science 314, 1461-1463 (2006).
7. Goyette, P., Labbe, C., Trinh, T. T., Xavier, R. J. & Rioux, J. D. Molecular pathogenesis of inflammatory bowel disease: genotypes, phenotypes and personalized medicine. Ann. Med. 39, 177-199 (2007).
8. Hampe, J. et al. A genome-wide association scan of nonsynonymous SNPs identifies a susceptibility variant for Crohn disease in ATG16L1. Nature Genet. 39, 207-211 (2007).
9. Libioulle, C. et al. Novel crohn disease locus identified by genome-wide association maps to a gene desert on 5p13.1 and modulates expression of PTGER4. PLoS Genet. 3, e58 (2007).
10. Peltekova, V. D. et al. Functional variants of OCTN cation transporter genes are associated with Crohn disease. Nature Genet. 36, 471-475 (2004).
11. Rioux, J. D. et al. Genetic variation in the 5q31 cytokine gene cluster confers susceptibility to Crohn disease. Nature Genet. 29, 223-228 (2001).
12. Rioux, J. D. et al. Genome-wide association study identifies new susceptibility loci for Crohn disease and implicates autophagy in disease pathogenesis. Nature Genet. 39, 596-604 (2007).
13. Silverberg, M. S. et al. Refined genomic localization and ethnic differences observed for the IBD5 association with Crohn's disease. Eur. J. Hum. Genet. 15, 328-335 (2007).
14. Yamazaki, K. et al. Single nucleotide polymorphisms in TNFSF15 confer susceptibility to Crohn's disease. Hum. Mol. Genet. 14, 3499-3506 (2005).
15. Gionchetti, P. et al. Prophylaxis of pouchitis onset with probiotic therapy: a double-blind, placebo-controlled trial. Gastroenterology 124, 1202-1209 (2003).
16. Sutherland, L. et al. Double blind, placebo controlled trial of metronidazole in Crohn's disease. Gut 32, 1071-1075 (1991).
17. Barnich, N. et al. CEACAM6 acts as a receptor for adherent-invasive E. coli, supporting ileal mucosa colonization in Crohn disease. J. Clin. Invest. 117, 1566-1574 (2007).
18. Darfeuille-Michaud, A. et al. Presence of adherent Escherichia coli strains in ileal mucosa of patients with Crohn's disease. Gastroenterology 115, 1405-1413 (1998).
19. Elson, C. O. et al. Experimental models of inflammatory bowel disease reveal innate, adaptive, and regulatory mechanisms of host dialogue with the microbiota. Immunol. Rev. 206, 260-276 (2005).
20. Onderdonk, A. B., Hermos, J. A. & Bartlett, J. G. The role of the intestinal microflora in experimental colitis. Am. J. Clin. Nutr. 30, 1819-1825 (1977).
21. Sellon, R. K. et al. Resident enteric bacteria are necessary for development of spontaneous colitis and immune system activation in interleukin-10-deficient mice. Infect. Immun. 66, 5224-5231 (1998).
22. Gill, S. R. et al. Metagenomic analysis of the human distal gut microbiome. Science 312, 1355-1359 (2006).
23. Buhner, S. et al. Genetic basis for increased intestinal permeability in families with Crohn's disease: role of CARD15 3020insC mutation? Gut 55, 342-347 (2006).
24. Irvine, E. J. & Marshall, J. K. Increased intestinal permeability precedes the onset of Crohn's disease in a subject with familial risk. Gastroenterology 119, 1740-1744 (2000).
25. May, G. R., Sutherland, L. R. & Meddings, J. B. Is small intestinal permeability really increased in relatives of patients with Crohn's disease? Gastroenterology 104, 1627-1632 (1993).
26. Soderholm, J. D. et al. Augmented increase in tight junction permeability by luminal stimuli in the non-inflamed ileum of Crohn's disease. Gut 50, 307-313 (2002).
27. Gassler, N. et al. Inflammatory bowel disease is associated with changes of enterocytic junctions. Am. J. Physiol. Gastrointest. Liver Physiol. 281, G216-G228 (2001).
28. Kabashima, K. et al. The prostaglandin receptor EP4 suppresses colitis, mucosal damage and CD4 cell activation in the gut. J. Clin. Invest. 109, 883-893 (2002).
29. Cario, E. et al. Lipopolysaccharide activates distinct signaling pathways in intestinal epithelial cell lines expressing Toll-like receptors. J. Immunol. 164, 966-972 (2000).
30. Hisamatsu, T. et al. CARD15/NOD2 functions as an antibacterial factor in human intestinal epithelial cells. Gastroenterology 124, 993-1000 (2003).
31. Yoshida, M. et al. Neonatal Fc receptor for IgG regulates mucosal immune responses to luminal bacteria. J. Clin. Invest. 116, 2142-2151 (2006).
32. Neish, A. S. et al. Prokaryotic regulation of epithelial responses by inhibition of IkB-a ubiquitination. Science 289, 1560-1563 (2000).
33. Kelly, D. et al. Commensal anaerobic gut bacteria attenuate inflammation by regulating nuclear-cytoplasmic shuttling of PPAR-γ and RelA. Nature Immunol. 5, 104-112 (2004).
34. Nenci, A. et al. Epithelial NEMO links innate immunity to chronic intestinal inflammation. Nature 446, 557-561 (2007).
35. Zaph, C. et al. Epithelial cell-intrinsic IKK-β expression regulates intestinal immune homeostasis. Nature 446, 552-556 (2007).
36. Wehkamp, J. et al. NOD2 (CARD15) mutations in Crohn's disease are associated with diminished mucosal alpha-defensin expression. Gut 53, 1658-1664 (2004).
37. Wehkamp, J. et al. Reduced Paneth cell α-defensins in ileal Crohn's disease. Proc. Natl Acad. Sci. USA 102, 18129-18134 (2005).
38. Mashimo, H., Wu, D. C., Podolsky, D. K. & Fishman, M. C. Impaired defense of intestinal mucosa in mice lacking intestinal trefoil factor. Science 274, 262-265 (1996).
39. McVay, L. D. et al. Absence of bacterially induced RELMβ reduces injury in the dextran sodium sulfate model of colitis. J. Clin. Invest. 116, 2914-2923 (2006).
40. Van der Sluis, M. et al. Muc2-deficient mice spontaneously develop colitis, indicating that MUC2 is critical for colonic protection. Gastroenterology 131, 117-129 (2006).
41. An, G. et al. Increased susceptibility to colitis and colorectal tumors in mice lacking core 3-derived O-glycans. J. Exp. Med. 204, 1417-1429 (2007).
42. Itoh, H., Beck, P. L., Inoue, N., Xavier, R. & Podolsky, D. K. A paradoxical reduction in susceptibility to colonic injury upon targeted transgenic ablation of goblet cells. J. Clin. Invest. 104, 1539-1547 (1999).
43. Salzman, N. H., Underwood, M. A. & Bevins, C. L. Paneth cells, defensins, and the commensal microbiota: A hypothesis on intimate interplay at the intestinal mucosa. Semin. Immunol. 19, 70-83 (2007).
44. Coombes, J. L. & Maloy, K. J. Control of intestinal homeostasis by regulatory T cells and dendritic cells. Semin. Immunol. 19, 116-126 (2007).
45. Chieppa, M., Rescigno, M., Huang, A. Y. & Germain, R. N. Dynamic imaging of dendritic cell extension into the small bowel lumen in response to epithelial cell TLR engagement. J. Exp. Med. 203, 2841-2852 (2006).
46. Niess, J. H. et al. CX3CR1-mediated dendritic cell access to the intestinal lumen and bacterial clearance. Science 307, 254-258 (2005).
47. Becker, C. et al. Constitutive p40 promoter activation and IL-23 production in the terminal ileum mediated by dendritic cells. J. Clin. Invest. 112, 693-706 (2003).
48. Hue, S. et al. Interleukin-23 drives innate and T cell-mediated intestinal inflammation. J. Exp. Med. 203, 2473-2483 (2006).
49. Mizoguchi, A. et al. Dependence of intestinal granuloma formation on unique myeloid DC-like cells. J. Clin. Invest. 117, 605-615 (2007).
50. Smith, P. D., Ochsenbauer-Jambor, C. & Smythies, L. E. Intestinal macrophages: unique effector cells of the innate immune system. Immunol. Rev. 206, 149-159 (2005).
51. Takeda, K. et al. Enhanced Th1 activity and development of chronic enterocolitis in mice devoid of Stat3 in macrophages and neutrophils. Immunity 10, 39-49 (1999).
52. Kamada, N. et al. Abnormally differentiated subsets of intestinal macrophage play a key role in Th1-dominant chronic colitis through excess production of IL-12 and IL-23 in response to bacteria. J. Immunol. 175, 6900-6908 (2005).
53. + T cells in a transfer model of colitis. J. Immunol. 161, 3256-3261 (1998).
54. Watanabe, T. et al. Nucleotide binding oligomerization domain 2 deficiency leads to dysregulated TLR2 signaling and induction of antigen-specific colitis. Immunity 25, 473-485 (2006).
55. Franchimont, D. et al. Deficient host-bacteria interactions in inflammatory bowel disease? The toll-like receptor (TLR)-4 Asp299gly polymorphism is associated with Crohn's disease and ulcerative colitis. Gut 53, 987-992 (2004).
56. Pierik, M. et al. Toll-like receptor-1, -2, and -6 polymorphisms influence disease extension in inflammatory bowel diseases. Inflamm. Bowel Dis. 12, 1-8 (2006).
57. Torok, H. P. et al. Crohn's disease is associated with a toll-like receptor-9 polymorphism. Gastroenterology 127, 365-366 (2004).
58. Inohara, N., Chamaillard, M.,McDonald, C. & Nunez, G. NOD-LRR proteins: role in host-microbial interactions and inflammatory disease. Annu. Rev. Biochem. 74, 355-383 (2005).
59. Kobayashi, K. et al. RICK/Rip2/CARDIAK mediates signalling for receptors of the innate and adaptive immune systems. Nature 416, 194-199 (2002).
60. Barnich, N. et al. GRIM-19 interacts with nucleotide oligomerization domain 2 and serves as downstream effector of anti-bacterial function in intestinal epithelial cells. J. Biol. Chem. 280, 19021-19026 (2005).
61. Chen, C. M., Gong, Y., Zhang, M. & Chen, J. J. Reciprocal cross-talk between Nod2 and TAK1 signaling pathways. J. Biol. Chem. 279, 25876-25882 (2004).
62. Mayor, A., Martinon, F., De Smedt, T., Petrilli, V. & Tschopp, J.Acrucial function of SGT1 and HSP90 in inflammasome activity links mammalian and plant innate immune responses. Nature Immunol. 8, 497-503 (2007).
63. McDonald, C. et al. A role for Erbin in the regulation of Nod2-dependent NF-κB signaling. J. Biol. Chem. 280, 40301-40309 (2005).
64. Pan, Q. et al. NF-κB-inducing kinase regulates selected gene expression in the Nod2 signaling pathway. Infect. Immun. 74, 2121-2127 (2006).
65. da Silva Correia, J., Miranda, Y., Leonard, N. & Ulevitch, R. SGT1 is essential for Nod1 activation. Proc. Natl Acad. Sci. USA 104, 6764-6769 (2007).
66. Bruey, J. M. et al. Bcl-2 and Bcl-XL regulate proinflammatory caspase-1 activation by interaction with NALP1. Cell 129, 45-56 (2007).
67. Kobayashi, K. S. et al. Nod2-dependent regulation of innate and adaptive immunity in the intestinal tract. Science 307, 731-734 (2005).
68. Li, J. et al. Regulation of IL-8 and IL-1β expression in Crohn's disease associated NOD2/CARD15 mutations. Hum. Mol. Genet. 13, 1715-1725 (2004).
69. Maeda, S. et al. Nod2 mutation in Crohn's disease potentiates NF-κB activity and IL-1β processing. Science 307, 734-738 (2005).
70. Gutierrez, M. G. et al. Protective role of autophagy against Vibrio cholerae cytolysin, a pore-forming toxin from V. cholerae. Proc. Natl Acad. Sci. USA 104, 1829-1834 (2007).
71. Mizushima, N. & Klionsky, D. J. Protein Turnover Via Autophagy: Implications for Metabolism. Annu. Rev. Nutr. 27, doi:10.1146/annurev.nutr.27.061406.093749 (2007).
72. Ogawa, M. et al. Escape of intracellular Shigella from autophagy. Science 307, 727-731 (2005).
73. Parkes, M. et al. Sequence variants in the autophagy gene IRGM and multiple other replicating loci contribute to Crohn's disease susceptibility. Nature Genet. 39, 830-832 (2007).
74. Singh, S. B., Davis, A. S., Taylor, G. A. & Deretic, V. Human IRGM induces autophagy to eliminate intracellular mycobacteria. Science 313, 1438-1441 (2006).
75. Taylor, G. A. IRG proteins: key mediators of interferon-regulated host resistance to intracellular pathogens. Cell. Microbiol. 9, 1099-1107 (2007).
76. phox-/- mice exhibit severe defects in NADPH oxidase regulation and oxidant-dependent bacterial killing. J. Exp. Med. 203, 1927-1937 (2006).
77. phox: the last NADPH oxidase subunit. Blood Cells Mol. Dis. 35, 291-302 (2005).
78. Stuart, L. M. & Ezekowitz, R. A. Phagocytosis: elegant complexity. Immunity 22, 539-550 (2005).
79. Mosmann, T. R., Cherwinski, H., Bond, M. W., Giedlin, M. A. & Coffman, R. L. Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J. Immunol. 136, 2348-2357 (1986).
80. Murphy, K. M. Fate vs choice: the immune system reloaded. Immunol. Res. 32, 193-200 (2005).
81. Weaver, C. T., Hatton, R. D., Mangan, P. R. & Harrington, L. E. IL-17 family cytokines and the expanding diversity of effector T cell lineages. Annu. Rev. Immunol. 25, 851-852 (2007).
82. Kastelein, R. A., Hunter, C. A. & Cua, D. J. Discovery and biology of IL-23 and IL-27: related but functionally distinct regulators of inflammation. Annu. Rev. Immunol. 25, 221-242 (2007).
83. H-17 cells in the circle of immunity and autoimmunity. Nature Immunol. 8, 345-350 (2007).
84. Laurence, A. et al. Interleukin-2 signaling via STAT5 constrains T helper 17 cell generation. Immunity 26, 371-381 (2007).
85. + T helper cells. Cell 126, 1121-1133 (2006).
86. Schnurr, M. et al. Extracellular nucleotide signaling by P2 receptors inhibits IL-12 and enhances IL-23 expression in human dendritic cells: a novel role for the cAMP pathway. Blood 105, 1582-1589 (2005).
87. Kullberg, M. C. et al. IL-23 plays a key role in Helicobacter hepaticus-induced T cell-dependent colitis. J. Exp. Med. 203, 2485-2494 (2006).
88. Uhlig, H. H. et al. Differential activity of IL-12 and IL-23 in mucosal and systemic innate immune pathology. Immunity 25, 309-318 (2006).
89. Yen, D. et al. IL-23 is essential for T cell-mediated colitis and promotes inflammation via IL-17 and IL-6. J. Clin. Invest. 116, 1310-1316 (2006).
90. Kinugasa, T., Sakaguchi, T., Gu, X. & Reinecker, H. C. Claudins regulate the intestinal barrier in response to immune mediators. Gastroenterology 118, 1001-1011 (2000).
91. Izcue, A., Coombes, J. L. & Powrie, F. Regulatory T cells suppress systemic and mucosal immune activation to control intestinal inflammation. Immunol. Rev. 212, 256-271 (2006).
92. Akbar, A. N., Vukmanovic-Stejic, M., Taams, L. S. & Macallan, D. C. The dynamic co-evolution of memory and regulatory CD41 T cells in the periphery. Nature Rev. Immunol. 7, 231-237 (2007).
93. Kim, J. M. & Rudensky, A. The role of the transcription factor Foxp3 in the development of regulatory T cells. Immunol. Rev. 212, 86-98 (2006).
94. + regulatory T cells in ulcerative colitis. Inflamm. Bowel Dis. 168, 1898-1909 (2006).
95. + T cells with regulatory function after interaction with intestinal epithelial cells. Gastroenterology 123, 1516-1526 (2002).
96. Mizoguchi, A. & Bhan, A. K. A case for regulatory B cells. J. Immunol. 176, 705-710 (2006).
97. Fuss, I. J. et al. Nonclassical CD1d-restricted NK T cells that produce IL-13 characterize an atypical Th2 response in ulcerative colitis. J. Clin. Invest. 113, 1490-1497 (2004).
98. Ley, R. E., Peterson, D. A. & Gordon, J. I. Ecological and evolutionary forces shaping microbial diversity in the human intestine. Cell 124, 837-848 (2006).