Inflammatory bowel disease: cause and immunobiology

Lancet

Volumn 369, Issue 9573, 2007, Pages 1627-1640

  Baumgart, Daniel C ^a,b   Carding, Simon R ^a,b  

^a CHARITÉ UNIVERSITÄTSMEDIZIN BERLIN   (Germany)

^b UNIVERSITY OF LEEDS   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

NUCLEOTIDE BINDING PROTEIN; PATTERN RECOGNITION RECEPTOR; TOLL LIKE RECEPTOR;

ADAPTIVE IMMUNITY; ANTIGEN PRESENTING CELL; ANTIGEN RECOGNITION; CELL AGGREGATION; DENDRITIC CELL; EFFECTOR CELL; ENTERITIS; ENVIRONMENTAL FACTOR; EPITHELIUM CELL; ETHNIC GROUP; GENETIC ANALYSIS; GENETIC SUSCEPTIBILITY; HOMEOSTASIS; HUMAN; IMMUNE DYSREGULATION; IMMUNOBIOLOGY; IMMUNOLOGICAL TOLERANCE; IMMUNOREGULATION; INNATE IMMUNITY; LIFESTYLE; LYMPHOID CELL; MACROPHAGE; MICROORGANISM; NATURAL KILLER T CELL; OLIGOMERIZATION; PRIORITY JOURNAL; PROTEIN INTERACTION; REGULATORY T LYMPHOCYTE; REVIEW; SEASONAL VARIATION; STOMACH MUCOSA; SYMBIOSIS; TWINS;

EID: 34248136828     PISSN: 01406736     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0140-6736(07)60750-8     Document Type: Review

References (169)

1. Baumgart D., and Sandborn W. Inflammatory bowel disease: clinical aspects and established and evolving therapies. Lancet 369 (2007) 1641-1657
2. Anonymous. Wilhelm Fabry (1560-1624): the other fabricius. JAMA 190 (1964) 933
3. Crohn B., Ginzburg L., and Oppenheimer G. Landmark article Oct 15, 1932: regional ileitis: a pathological and clinical entity, by Burril B Crohn, Leon Ginzburg, and Gordon D Oppenheimer. JAMA 251 (1984) 73-79
4. Wilks S. Morbid appearances in the intestine of Miss Bankes. London Medical Times & Gazette 2 (1859) 264
5. Loftus Jr. E. Clinical epidemiology of inflammatory bowel disease: incidence, prevalence, and environmental influences. Gastroenterology 126 (2004) 1504-1517
6. Sedlack R., Whisnant J., Elveback L., and Kurland L. Incidence of Crohn's disease in Olmsted County, Minnesota, 1935-75. Am J Epidemiol 112 (1980) 759-763
7. Loftus C., Loftus Jr. E., Harmsen W., et al. Update on the incidence and prevalence of Crohn's disease and ulcerative colitis in Olmsted County, Minnesota, 1940-2000. Inflamm Bowel Dis (2006). published online Dec 19. DOI 10.1002/ibd.20029
8. Loftus Jr. E., Silverstein M., Sandborn W., Tremaine W., Harmsen W., and Zinsmeister A. Ulcerative colitis in Olmsted County, Minnesota, 1940-1993: incidence, prevalence, and survival. Gut 46 (2000) 336-343
9. Loftus Jr. E., Silverstein M., Sandborn W., Tremaine W., Harmsen W., and Zinsmeister A. Crohn's disease in Olmsted County, Minnesota, 1940-1993: incidence, prevalence, and survival. Gastroenterology 114 (1998) 1161-1168
10. Binder V., Both H., Hansen P., Hendriksen C., Kreiner S., and Torp-Pedersen K. Incidence and prevalence of ulcerative colitis and Crohn's disease in the County of Copenhagen, 1962 to 1978. Gastroenterology 83 (1982) 563-568
11. Langholz E., Munkholm P., Nielsen O., Kreiner S., and Binder V. Incidence and prevalence of ulcerative colitis in Copenhagen county from 1962 to 1987. Scand J Gastroenterol 26 (1991) 1247-1256
12. Munkholm P., Langholz E., Nielsen O., Kreiner S., and Binder V. Incidence and prevalence of Crohn's disease in the county of Copenhagen, 1962-87: a sixfold increase in incidence. Scand J Gastroenterol 27 (1992) 609-614
13. Bernstein C., Blanchard J., Rawsthorne P., and Wajda A. Epidemiology of Crohn's disease and ulcerative colitis in a central Canadian province: a population-based study. Am J Epidemiol 149 (1999) 916-924
14. Blanchard J., Bernstein C., Wajda A., and Rawsthorne P. Small-area variations and sociodemographic correlates for the incidence of Crohn's disease and ulcerative colitis. Am J Epidemiol 154 (2001) 328-335
15. Lapidus A., Bernell O., Hellers G., Persson P., and Lofberg R. Incidence of Crohn's disease in Stockholm County 1955-89. Gut 41 (1997) 480-486
16. Lapidus A. Crohn's disease in Stockholm County during 1990-2001: an epidemiological update. World J Gastroenterol 12 (2006) 75-81
17. Kurata J., Kantor-Fish S., Frankl H., Godby P., and Vadheim C. Crohn's disease among ethnic groups in a large health maintenance organization. Gastroenterology 102 (1992) 1940-1948
18. Nguyen G., Torres E., Regueiro M., et al. Inflammatory bowel disease characteristics among African Americans, Hispanics, and non-Hispanic Whites: characterization of a large North American cohort. Am J Gastroenterol 101 (2006) 1012-1023
19. Heresbach D., Gulwani-Akolkar B., Lesser M., et al. Anticipation in Crohn's disease may be influenced by gender and ethnicity of the transmitting parent. Am J Gastroenterol 93 (1998) 2368-2372
20. Hampe J., Heymann K., Kruis W., Raedler A., Folsch U., and Schreiber S. Anticipation in inflammatory bowel disease: a phenomenon caused by an accumulation of confounders. Am J Med Genet 92 (2000) 178-183
21. Niv Y., Abuksis G., and Fraser G. Epidemiology of ulcerative colitis in Israel: a survey of Israeli kibbutz settlements. Am J Gastroenterol 95 (2000) 693-698
22. Grossman A., Fireman Z., Lilos P., Novis B., Rozen P., and Gilat T. Epidemiology of ulcerative colitis in the Jewish population of central Israel 1970-1980. Hepatogastroenterology 36 (1989) 193-197
23. Leong R., Lau J., and Sung J. The epidemiology and phenotype of Crohn's disease in the Chinese population. Inflamm Bowel Dis 10 (2004) 646-651
24. Zheng J., Zhu X., Huangfu Z., Gao Z., Guo Z., and Wang Z. Crohn's disease in mainland China: a systematic analysis of 50 years of research. Chin J Dig Dis 6 (2005) 175-181
25. Russell R., and Satsangi J. IBD: a family affair. Best Pract Res Clin Gastroenterol 18 (2004) 525-539
26. Satsangi J., Grootscholten C., Holt H., and Jewell D. Clinical patterns of familial inflammatory bowel disease. Gut 38 (1996) 738-741
27. Tysk C., Lindberg E., Jarnerot G., and 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 (1988) 990-996
28. Thompson N., Driscoll R., Pounder R., and Wakefield A. Genetics versus environment in inflammatory bowel disease: results of a British twin study. BMJ 312 (1996) 95-96
29. Orholm M., Binder V., Sorensen T., Rasmussen L., and Kyvik K. Concordance of inflammatory bowel disease among Danish twins: results of a nationwide study. Scand J Gastroenterol 35 (2000) 1075-1081
30. Gaya D., Russell R., Nimmo E., and Satsangi J. New genes in inflammatory bowel disease: lessons for complex diseases?. Lancet 367 (2006) 1271-1284
31. Hugot J., Laurent-Puig P., Gower-Rousseau C., et al. Mapping of a susceptibility locus for Crohn's disease on chromosome 16. Nature 379 (1996) 821-823
32. Satsangi J., Parkes M., Louis E., et al. Two stage genome-wide search in inflammatory bowel disease provides evidence for susceptibility loci on chromosomes 3, 7 and 12. Nat Genet 14 (1996) 199-202
33. Cho J., Nicolae D., Gold L., et al. Identification of novel susceptibility loci for inflammatory bowel disease on chromosomes 1p, 3q, and 4q: evidence for epistasis between 1p and inflammatory bowel disease1. Proc Natl Acad Sci USA 95 (1998) 7502-7507
34. Hampe J., Shaw S., Saiz R., et al. Linkage of inflammatory bowel disease to human chromosome 6p. Am J Hum Genet 65 (1999) 1647-1655
35. Ma Y., Ohmen J., Li Z., et al. A genome-wide search identifies potential new susceptibility loci for Crohn's disease. Inflamm Bowel Dis 5 (1999) 271-278
36. Duerr R., Barmada M., Zhang L., Pfutzer R., and Weeks D. High-density genome scan in Crohn disease shows confirmed linkage to chromosome 14q11-12. Am J Hum Genet 66 (2000) 1857-1862
37. Rioux J., Silverberg M., Daly M., et al. Genomewide search in Canadian families with inflammatory bowel disease reveals two novel susceptibility loci. Am J Hum Genet 66 (2000) 1863-1870
38. Williams C., Kocher K., Lander E., Daly M., and Rioux J. Using a genome-wide scan and meta-analysis to identify a novel IBD locus and confirm previously identified IBD loci. Inflamm Bowel Dis 8 (2002) 375-381
39. Paavola-Sakki P., Ollikainen V., Helio T., et al. Genome-wide search in Finnish families with inflammatory bowel disease provides evidence for novel susceptibility loci. Eur J Hum Genet 11 (2003) 112-120
40. Vermeire S. DLG5 and OCTN. Inflamm Bowel Dis 10 (2004) 888-890
41. Barmada M., Brant S., Nicolae D., et al. A genome scan in 260 inflammatory bowel disease-affected relative pairs. Inflamm Bowel Dis 10 (2004) 15-22
42. Duerr R., Taylor K., Brant S., et al. A genome-wide association study identifies IL23R as an inflammatory bowel disease gene. Science (Oct 26, 2006). published online DOI:10.1126/science.1135245
43. Vermeire S., and Rutgeerts P. Current status of genetics research in inflammatory bowel disease. Genes Immunol 6 (2005) 637-645
44. Hampe J., Schreiber S., Shaw S., et al. A genomewide analysis provides evidence for novel linkages in inflammatory bowel disease in a large European cohort. Am J Hum Genet 64 (1999) 808-816
45. Stoll M., Corneliussen B., Costello C., et al. Genetic variation in DLG5 is associated with inflammatory bowel disease. Nat Genet 36 (2004) 476-480
46. Peltekova V., Wintle R., Rubin L., et al. Functional variants of OCTN cation transporter genes are associated with Crohn disease. Nat Genet 36 (2004) 471-475
47. Tamai I., Yabuuchi H., Nezu J., et al. Cloning and characterization of a novel human pH-dependent organic cation transporter, OCTN1. FEBS Lett 419 (1997) 107-111
48. Wu X., Prasad P., Leibach F., and Ganapathy V. cDNA sequence, transport function, and genomic organization of human OCTN2, a new member of the organic cation transporter family. Biochem Biophys Res Commun 246 (1998) 589-595
49. Lahjouji K., Mitchell G., and Qureshi I. Carnitine transport by organic cation transporters and systemic carnitine deficiency. Mol Genet Metab 73 (2001) 287-297
50. Martinon F., and Tschopp J. NLRs join TLRs as innate sensors of pathogens. Trends Immunol 26 (2005) 447-454
51. Inohara N., and Nunez G. NODs: intracellular proteins involved in inflammation and apoptosis. Nat Rev Immunol 3 (2003) 371-382
52. Girardin S., Boneca I., Carneiro L., et al. Nod1 detects a unique muropeptide from gram-negative bacterial peptidoglycan. Science 300 (2003) 1584-1587
53. Girardin S., Boneca I., Viala J., et al. Nod2 is a general sensor of peptidoglycan through muramyl dipeptide (MDP) detection. J Biol Chem 278 (2003) 8869-8872
54. Chamaillard M., Hashimoto M., Horie Y., et al. An essential role for NOD1 in host recognition of bacterial peptidoglycan containing diaminopimelic acid. Nat Immunol 4 (2003) 702-707
55. Akira S., and Takeda K. Toll-like receptor signalling. Nat Rev Immunol 4 (2004) 499-511
56. Strober W., Murray P., Kitani A., and Watanabe F. Signalling pathways and molecular interactions of NOD1 and NOD2. Nat Rev Immunol 6 (2006) 9-19
57. van Heel D., Fisher S., Kirby A., Daly M., Rioux J., and Lewis C. Inflammatory bowel disease susceptibility loci defined by genome scan meta-analysis of 1952 affected relative pairs. Hum Mol Genet 13 (2004) 763-770
58. Cummings J., and Jewell D. Clinical implications of inflammatory bowel disease genetics on phenotype. Inflamm Bowel Dis 11 (2005) 56-61
59. Hugot J., Chamaillard M., Zouali H., et al. Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease. Nature 411 (2001) 599-603
60. Inohara N., Ogura Y., Fontalba A., et al. Host recognition of bacterial muramyl dipeptide mediated through NOD2. Implications for Crohn's disease. J Biol Chem 278 (2003) 5509-5512
61. Abbott D., Wilkins A., Asara J., and Cantley L. The Crohn's disease protein, NOD2, requires RIP2 in order to induce ubiquitinylation of a novel site on NEMO. Curr Biol 14 (2004) 2217-2227
62. Watanabe T., Kitani A., Murray P., and Strober W. NOD2 is a negative regulator of Toll-like receptor 2-mediated T helper type 1 responses. Nat Immunol 5 (2004) 800-808
63. Maeda S., Hsu L., Liu H., et al. Nod2 mutation in Crohn's disease potentiates NF-kappaB activity and IL-1beta processing. Science 307 (2005) 734-738
64. Moum B., Aadland E., Ekbom A., and Vatn M. Seasonal variations in the onset of ulcerative colitis. Gut 38 (1996) 376-378
65. Sonnenberg A., Jacobsen S., and Wasserman I. Periodicity of hospital admissions for inflammatory bowel disease. Am J Gastroenterol 89 (1994) 847-851
66. Soncini M., Triossi O., Leo P., et al. Seasonal patterns of hospital treatment for inflammatory bowel disease in Italy. Digestion 73 (2006) 1-8
67. Lewis J., Aberra F., Lichtenstein G., Bilker W., Brensinger C., and Strom B. Seasonal variation in flares of inflammatory bowel disease. Gastroenterology 126 (2004) 665-673
68. Schack-Nielsen L., and Michaelsen K. Breast feeding and future health. Curr Opin Clin Nutr Metab Care 9 (2006) 289-296
69. Klement E., Cohen R., Boxman J., Joseph A., and Reif S. Breastfeeding and risk of inflammatory bowel disease: a systematic review with meta-analysis. Am J Clin Nutr 80 (2004) 1342-1352
70. Kane S., and Lemieux N. The role of breastfeeding in postpartum disease activity in women with inflammatory bowel disease. Am J Gastroenterol 100 (2005) 102-105
71. Riordan A., Ruxton C., and Hunter J. A review of associations between Crohn's disease and consumption of sugars. Eur J Clin Nutr 52 (1998) 229-238
72. Geerling B., Dagnelie P., Badart-Smook A., Russel M., Stockbrugger R., and Brummer R. Diet as a risk factor for the development of ulcerative colitis. Am J Gastroenterol 95 (2000) 1008-1013
73. Weylandt K., and Kang J. Rethinking lipid mediators. Lancet 366 (2005) 618-620
74. Desai H., and Gupte P. Increasing incidence of Crohn's disease in India: is it related to improved sanitation?. Indian J Gastroenterol 24 (2005) 23-24
75. Kinra S., Davey S., Jeffreys M., Gunnell D., Galobardes B., and McCarron P. Association between sibship size and allergic diseases in the Glasgow Alumni Study. Thorax 61 (2006) 48-53
76. Hampe J., Heymann K., Krawczak M., and Schreiber S. Association of inflammatory bowel disease with indicators for childhood antigen and infection exposure. Int J Colorectal Dis 18 (2003) 413-417
77. Gent A., Hellier M., Grace R., Swarbrick E., and Coggon D. Inflammatory bowel disease and domestic hygiene in infancy. Lancet 343 (1994) 766-767
78. McCormick P., and Manning D. Chronic inflammatory bowel disease and the 'over-clean' environment: rarity in the Irish 'traveller' community. Ir Med J 94 (2001) 203-204
79. Mawdsley J., and Rampton D. Psychological stress in IBD: new insights into pathogenic and therapeutic implications. Gut 54 (2005) 1481-1491
80. Cosnes J. Tobacco and IBD: relevance in the understanding of disease mechanisms and clinical practice. Best Pract Res Clin Gastroenterol 18 (2004) 481-496
81. McGrath J., McDonald J., and Macdonald J. Transdermal nicotine for induction of remission in ulcerative colitis. Cochrane Database Syst Rev 4 (2004) CD004722.
82. Ingram J., Thomas G., Rhodes J., et al. A randomized trial of nicotine enemas for active ulcerative colitis. Clin Gastroenterol Hepatol 3 (2005) 1107-1114
83. Ekbom A., Wakefield A., Zack M., and Adami H. Perinatal measles infection and subsequent Crohn's disease. Lancet 344 (1994) 508-510
84. Robertson D., and Sandler R. Measles virus and Crohn's disease: a critical appraisal of the current literature. Inflamm Bowel Dis 7 (2001) 51-57
85. Sartor R. Does Mycobacterium avium subspecies paratuberculosis cause Crohn's disease?. Gut 54 (2005) 896-898
86. Garcia Rodriguez L., Ruigomez A., and Panes J. Acute gastroenteritis is followed by an increased risk of inflammatory bowel disease. Gastroenterology 130 (2006) 1588-1594
87. Swidsinski A., Ladhoff A., Pernthaler A., et al. Mucosal flora in inflammatory bowel disease. Gastroenterology 122 (2002) 44-54
88. Darfeuille-Michaud A., Boudeau J., Bulois P., et al. High prevalence of adherent-invasive Escherichia coli associated with ileal mucosa in Crohn's disease. Gastroenterology 127 (2004) 412-421
89. Davis R., Kramarz P., Bohlke K., et al. Measles-mumps-rubella and other measles-containing vaccines do not increase the risk for inflammatory bowel disease: a case-control study from the Vaccine Safety Datalink project. Arch Pediatr Adolesc Med 155 (2001) 354-359
90. Godet P., May G., and Sutherland L. Meta-analysis of the role of oral contraceptive agents in inflammatory bowel disease. Gut 37 (1995) 668-673
91. Koutroubakis I., Vlachonikolis I., and Kouroumalis E. Role of appendicitis and appendectomy in the pathogenesis of ulcerative colitis: a critical review. Inflamm Bowel Dis 8 (2002) 277-286
92. Radford-Smith G., Edwards J., Purdie D., et al. Protective role of appendicectomy on onset and severity of ulcerative colitis and Crohn's disease. Gut 51 (2002) 808-813
93. Cosnes J., Seksik P., Nion-Larmurier I., Beaugerie L., and Gendre J. Prior appendectomy and the phenotype and course of Crohn's disease. World J Gastroenterol 12 (2006) 1235-1242
94. Andersson R., Olaison G., Tysk C., and Ekbom A. Appendectomy is followed by increased risk of Crohn's disease. Gastroenterology 124 (2003) 40-46
95. Hughes J., Hellmann J., Ricketts T., and Bohannan B. Counting the uncountable: statistical approaches to estimating microbial diversity. Appl Environ Microbiol 67 (2001) 4399-4406
96. Berg R. The indigenous gastrointestinal microflora. Trends Microbiol 4 (1996) 430-435
97. Cruickshank S., McVay L., Baumgart D., Felsburg P., and Carding S. Colonic epithelial cell mediated suppression of CD4 T cell activation. Gut 53 (2004) 678-684
98. Hooper L., Wong M., Thelin A., Hansson L., Falk P., and Gordon J. Molecular analysis of commensal host-microbial relationships in the intestine. Science 291 (2001) 881-884
99. Kraus T., and Mayer L. Oral tolerance and inflammatory bowel disease. Curr Opin Gastroenterol 21 (2005) 692-696
100. Baumgart D., and Dignass A. Intestinal barrier function. Curr Opin Clin Nutr Metab Care 5 (2002) 685-694
101. Buisine M., Desreumaux P., Leteurtre E., et al. Mucin gene expression in intestinal epithelial cells in Crohn's disease. Gut 49 (2001) 544-551
102. Smithson J., Campbell A., Andrews J., Milton J., Pigott R., and Jewell D. Altered expression of mucins throughout the colon in ulcerative colitis. Gut 40 (1997) 234-240
103. Elphick D., and Mahida Y. Paneth cells: their role in innate immunity and inflammatory disease. Gut 54 (2005) 1802-1809
104. Selsted M., and Ouellette A. Mammalian defensins in the antimicrobial immune response. Nat Immunol 6 (2005) 551-557
105. Brogden K. Antimicrobial peptides: pore formers or metabolic inhibitors in bacteria?. Nat Rev Microbiol 3 (2005) 238-250
106. Hershberg R. The epithelial cell cytoskeleton and intracellular trafficking. V. Polarized compartmentalization of antigen processing and Toll-like receptor signaling in intestinal epithelial cells. Am J Physiol Gastrointest Liver Physiol 283 (2002) G833-G839
107. Iwasaki A., and Medzhitov R. Toll-like receptor control of the adaptive immune responses. Nat Immunol 5 (2004) 987-995
108. Hornef M., Frisan T., Vandewalle A., Normark S., and Richter-Dahlfors A. Toll-like receptor 4 resides in the Golgi apparatus and colocalizes with internalized lipopolysaccharide in intestinal epithelial cells. J Exp Med 195 (2002) 559-570
109. Rakoff-Nahoum S., Paglino J., Eslami-Varzaneh F., Edberg S., and Medzhitov R. Recognition of commensal microflora by toll-like receptors is required for intestinal homeostasis. Cell 118 (2004) 229-241
110. Cario E., Gerken G., and Podolsky D. Toll-like receptor 2 enhances ZO-1-associated intestinal epithelial barrier integrity via protein kinase C. Gastroenterology 127 (2004) 224-238
111. Rosenstiel P., Fantini M., Brautigam K., et al. TNF-alpha and IFN-gamma regulate the expression of the NOD2 (CARD15) gene in human intestinal epithelial cells. Gastroenterology 124 (2003) 1001-1009
112. Berrebi D., Maudinas R., Hugot J., et al. Card15 gene overexpression in mononuclear and epithelial cells of the inflamed Crohn's disease colon. Gut 52 (2003) 840-846
113. Lala S., Ogura Y., Osborne C., et al. Crohn's disease and the NOD2 gene: a role for paneth cells. Gastroenterology 125 (2003) 47-57
114. Ogura Y., Lala S., Xin W., et al. Expression of NOD2 in Paneth cells: a possible link to Crohn's ileitis. Gut 52 (2003) 1591-1597
115. Ogura Y., Inohara N., Benito A., Chen F., Yamaoka S., and Nunez G. Nod2, a Nod1/Apaf-1 family member that is restricted to monocytes and activates NF-kappaB. J Biol Chem 276 (2001) 4812-4818
116. Stockinger S., Reutterer B., Schaljo B., et al. IFN regulatory factor 3-dependent induction of type I IFNs by intracellular bacteria is mediated by a TLR- and Nod2-independent mechanism. J Immunol 173 (2004) 7416-7425
117. Kobayashi K., Chamaillard M., Ogura Y., et al. Nod2-dependent regulation of innate and adaptive immunity in the intestinal tract. Science 307 (2005) 731-734
118. Wilson C., Ouellette A., Satchell D., et al. Regulation of intestinal alpha-defensin activation by the metalloproteinase matrilysin in innate host defense. Science 286 (1999) 113-117
119. Garabedian E., Roberts L., McNevin M., and Gordon J. Examining the role of Paneth cells in the small intestine by lineage ablation in transgenic mice. J Biol Chem 272 (1997) 23729-23740
120. Mach J., Hshieh T., Hsieh D., Grubbs N., and Chervonsky A. Development of intestinal M cells. Immunol Rev 206 (2005) 177-189
121. Niess J., Brand S., Gu X., et al. CX3CR1-mediated dendritic cell access to the intestinal lumen and bacterial clearance. Science 307 (2005) 2545-2548
122. Rescigno M., Urbano M., Valzasina B., et al. Dendritic cells express tight junction proteins and penetrate gut epithelial monolayers to sample bacteria. Nat Immunol 2 (2001) 361-367
123. Banchereau J., and Steinman R. Dendritic cells and the control of immunity. Nature 392 (1998) 245-252
124. Hart A., Lammers K., Brigidi P., et al. Modulation of human dendritic cell phenotype and function by probiotic bacteria. Gut 53 (2004) 1602-1609
125. Steinman R., and Nussenzweig M. Avoiding horror autotoxicus: the importance of dendritic cells in peripheral T cell tolerance. Proc Natl Acad Sci USA 99 (2002) 351-358
126. West M., Wallin R., Matthews S., et al. Enhanced dendritic cell antigen capture via toll-like receptor-induced actin remodeling. Science 305 (2004) 1153-1157
127. Degli-Esposti M., and Smyth M. Close encounters of different kinds: dendritic cells and NK cells take centre stage. Nat Rev Immunol 5 (2005) 112-124
128. Soderholm J., Olaison G., Peterson K., et al. Augmented increase in tight junction permeability by luminal stimuli in the non-inflamed ileum of Crohn's disease. Gut 50 (2002) 307-313
129. Irvine E., and Marshall J. Increased intestinal permeability precedes the onset of Crohn's disease in a subject with familial risk. Gastroenterology 119 (2000) 1740-1744
130. Buhner S., Buning C., Genschel J., et al. Genetic basis for increased intestinal permeability in families with Crohn's disease: role of CARD15 3020insC mutation?. Gut 55 (2006) 342-347
131. Sun Y., Fihn B., Sjovall H., and Jodal M. Enteric neurones modulate the colonic permeability response to luminal bile acids in rat colon in vivo. Gut 53 (2004) 362-367
132. Ma T., Iwamoto G., Hoa N., et al. TNF-alpha-induced increase in intestinal epithelial tight junction permeability requires NF-kappa B activation. Am J Physiol Gastrointest Liver Physiol 286 (2004) G367-G376
133. +-ATPase. J Clin Invest 110 (2002) 1739-1747
134. Heller F., Florian P., Bojarski C., et al. Interleukin-13 is the key effector Th2 cytokine in ulcerative colitis that affects epithelial tight junctions, apoptosis, and cell restitution. Gastroenterology 129 (2005) 550-564
135. Cario E., and Podolsky D. Differential alteration in intestinal epithelial cell expression of toll-like receptor 3 (TLR3) and TLR4 in inflammatory bowel disease. Infect Immun 68 (2000) 7010-7017
136. Akhtar M., Watson J., Nazli A., and McKay D. Bacterial DNA evokes epithelial IL-8 production by a MAPK-dependent, NF-kappaB-independent pathway. FASEB J 17 (2003) 1319-1321
137. Rhee S., Im E., Riegler M., Kokkotou E., O'brien M., and Pothoulakis C. Pathophysiological role of Toll-like receptor 5 engagement by bacterial flagellin in colonic inflammation. Proc Natl Acad Sci USA 102 (2005) 13610-13615
138. Franchimont D., Vermeire S., El H., 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 (2004) 987-992
139. Hart A., Al-Hassi H., Rigby R., et al. Characteristics of intestinal dendritic cells in inflammatory bowel diseases. Gastroenterology 129 (2005) 50-65
140. Malmstrom V., Shipton D., Singh B., et al. CD134L expression on dendritic cells in the mesenteric lymph nodes drives colitis in T cell-restored SCID mice. J Immunol 166 (2001) 6972-6981
141. Leithauser F., Trobonjaca Z., Moller P., and Reimann J. Clustering of colonic lamina propria CD4(+) T cells to subepithelial dendritic cell aggregates precedes the development of colitis in a murine adoptive transfer model. Lab Invest 81 (2001) 1339-1349
142. Krajina T., Leithauser F., Moller P., Trobonjaca Z., and Reimann J. Colonic lamina propria dendritic cells in mice with CD4+ T cell-induced colitis. Eur J Immunol 33 (2003) 1073-1083
143. Ashcroft A., Cruickshank S., Croucher P., et al. Colonic dendritic cells, intestinal inflammation, and T cell-mediated bone destruction are modulated by recombinant osteoprotegerin. Immunity 19 (2003) 849-861
144. Baumgart D., Metzke D., Wiedenmann B., and Dignass A. Activated dendritic cells are significantly increased in inflamed intestinal mucosa of inflammatory bowel disease patients. Gastroenterology 126 (2004) A159
145. Baumgart D., Metzke D., Schmitz J., et al. Patients with active inflammatory bowel disease lack immature peripheral blood plasmacytoid and myeloid dendritic cells. Gut 54 (2005) 228-236
146. Papadakis K., Zhu D., Prehn J., et al. Dominant role for TL1A/DR3 pathway in IL-12 plus IL-18-induced IFN-gamma production by peripheral blood and mucosal CCR9+ T lymphocytes. J Immunol 174 (2005) 4985-4990
147. van de W., Corazza N., Allez M., et al. Delineation of a CD1d-restricted antigen presentation pathway associated with human and mouse intestinal epithelial cells. Gastroenterology 124 (2003) 1420-1431
148. Nakazawa A., Dotan I., Brimnes J., et al. The expression and function of costimulatory molecules B7H and B7-H1 on colonic epithelial cells. Gastroenterology 126 (2004) 1347-1357
149. Srikrishna G., Turovskaya O., Shaikh R., et al. Carboxylated glycans mediate colitis through activation of NF-kappa B. J Immunol 175 (2005) 5412-5422
150. Hokama A., Mizoguchi E., Sugimoto K., et al. Induced reactivity of intestinal CD4(+) T cells with an epithelial cell lectin, galectin-4, contributes to exacerbation of intestinal inflammation. Immunity 20 (2004) 681-693
151. Ina K., Itoh J., Fukushima K., et al. Resistance of Crohn's disease T cells to multiple apoptotic signals is associated with a Bcl-2/Bax mucosal imbalance. J Immunol 163 (1999) 1081-1090
152. Van den Brande J., Braat H., van den Brink G., et al. Infliximab but not etanercept induces apoptosis in lamina propria T-lymphocytes from patients with Crohn's disease. Gastroenterology 124 (2003) 1774-1785
153. Martin B., Banz A., Bienvenu B., et al. Suppression of CD4+ T lymphocyte effector functions by CD4+CD25+ cells in vivo. J Immunol 172 (2004) 3391-3398
154. Neurath M., Weigmann B., Finotto S., et al. The transcription factor T-bet regulates mucosal T cell activation in experimental colitis and Crohn's disease. J Exp Med 195 (2002) 1129-1143
155. Langrish C., Chen Y., Blumenschein W., et al. IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. J Exp Med 201 (2005) 233-240
156. Fuss I., Becker C., Yang Z., et al. Both IL-12p70 and IL-23 are synthesized during active Crohn's disease and are down-regulated by treatment with anti-IL-12 p40 monoclonal antibody. Inflamm Bowel Dis 12 (2006) 9-15
157. Fuss I., Heller F., Boirivant M., et al. Nonclassical CD1d-restricted NK T cells that produce IL-13 characterize an atypical Th2 response in ulcerative colitis. J Clin Invest 113 (2004) 1490-1497
158. Mangan P., Harrington L., O'Quinn D., et al. Transforming growth factor-beta induces development of the T(H)17 lineage. Nature 441 (2006) 231-234
159. Veldhoen M., Hocking R., Atkins C., Locksley R., and Stockinger B. TGFbeta in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells. Immunity 24 (2006) 179-189
160. Wang H., Yu M., Ochani M., et al. Nicotinic acetylcholine receptor alpha7 subunit is an essential regulator of inflammation. Nature 421 (2003) 384-388
161. Neunlist M., Aubert P., Toquet C., et al. Changes in chemical coding of myenteric neurones in ulcerative colitis. Gut 52 (2003) 84-90
162. Furlan R., Ardizzone S., Palazzolo L., et al. Sympathetic overactivity in active ulcerative colitis: effects of clonidine. Am J Physiol Regul Integr Comp Physiol 290 (2006) R224-R232
163. Demaude J., Salvador-Cartier C., Fioramonti J., Ferrier L., and Bueno L. Phenotypic changes in colonocytes following acute stress or activation of mast cells in mice: implications for delayed epithelial barrier dysfunction. Gut 55 (2006) 655-661
164. Charo I., and Ransohoff R. The many roles of chemokines and chemokine receptors in inflammation. N Engl J Med 354 (2006) 610-621
165. Goebel S., Huang M., Davis W., et al. VEGF-A stimulation of leukocyte adhesion to colonic microvascular endothelium: implications for inflammatory bowel disease. Am J Physiol Gastrointest Liver Physiol 290 (2006) G648-G654
166. Keshavarzian A., Banan A., Farhadi A., et al. Increases in free radicals and cytoskeletal protein oxidation and nitration in the colon of patients with inflammatory bowel disease. Gut 52 (2003) 720-728
167. Leeb S., Vogl D., Gunckel M., et al. Reduced migration of fibroblasts in inflammatory bowel disease: role of inflammatory mediators and focal adhesion kinase. Gastroenterology 125 (2003) 1341-1354
168. Theiss A., Simmons J., Jobin C., and Lund P. Tumor necrosis factor (TNF) alpha increases collagen accumulation and proliferation in intestinal myofibroblasts via TNF receptor 2. J Biol Chem 280 (2005) 36099-36109
169. Kirkegaard T., Hansen A., Bruun E., and Brynskov J. Expression and localisation of matrix metalloproteinases and their natural inhibitors in fistulae of patients with Crohn's disease. Gut 53 (2004) 701-709