Current view of the immunopathogenesis in inflammatory bowel disease and its implications for therapy

World Journal of Gastroenterology

Volumn 14, Issue 13, 2008, Pages 1972-1980

  Torres, M I ^a   Rios A ^b  

^a UNIVERSITY OF JAÉN   (Spain)

^b UNIVERSITY OF GRANADA   (Spain)

Author keywords

Crohn's disease; Cytokines; Inflammatory bowel disease; Mucosal inflammation; Tolerance; Ulcerative colitis

Indexed keywords

CALCINEURIN INHIBITOR; CASPASE RECRUITMENT DOMAIN PROTEIN 15; CASPASE RECRUITMENT DOMAIN PROTEIN 4; CD3 ANTIBODY; CELL ADHESION MOLECULE; CYCLOSPORIN; CYTOKINE; FLAVONOID; HLA ANTIGEN; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INFLIXIMAB; INTERLEUKIN 17; INTERLEUKIN 23; INTERLEUKIN 6; MONOCLONAL ANTIBODY; MORIN; POLYUNSATURATED FATTY ACID; PREBIOTIC AGENT; PROBIOTIC AGENT; REACTIVE OXYGEN METABOLITE; SALAZOSULFAPYRIDINE; TACROLIMUS; THROMBOCYTE ACTIVATING FACTOR ANTAGONIST; TOLL LIKE RECEPTOR 4; TUMOR NECROSIS FACTOR ALPHA ANTIBODY; TUMOR NECROSIS FACTOR ALPHA INHIBITOR; UR 12746; VASCULAR ENDOTHELIAL GROWTH INHIBITOR; VILISILIZUMAB;

ANTIINFLAMMATORY ACTIVITY; ANTIOXIDANT ACTIVITY; CROHN DISEASE; CYTOKINE RELEASE; DIET THERAPY; DIETARY FIBER; DRUG EFFICACY; DRUG ERUPTION; DRUG FEVER; DRUG INDUCED HEADACHE; DRUG MECHANISM; EDITORIAL; ENTERITIS; ENVIRONMENTAL FACTOR; ENZYME INHIBITION; GASTROINTESTINAL MUCOSA; GENETIC ASSOCIATION; GENETIC SUSCEPTIBILITY; HISTOPATHOLOGY; HOST SUSCEPTIBILITY; HUMAN; IMMUNE RESPONSE; IMMUNOMODULATION; IMMUNOPATHOGENESIS; IMMUNOSUPPRESSIVE TREATMENT; INCIDENCE; INNATE IMMUNITY; MUCOSAL IMMUNITY; NAUSEA; NONHUMAN; NUTRITIONAL DEFICIENCY; PATHOPHYSIOLOGY; PREVALENCE; SKIN MANIFESTATION; ULCERATIVE COLITIS; VOMITING;

EID: 44849098365     PISSN: 10079327     EISSN: None     Source Type: Journal    
DOI: 10.3748/wjg.14.1972     Document Type: Editorial

References (100)

1. Wittig BM, Zeitz M. The gut as an organ of immunology. Int J Colorectal Dis 2003; 18: 181-187
2. Jump RL, Levine AD. Mechanisms of natural tolerance in the intestine: implications for inflammatory bowel disease. Inflamm Bowel Dis 2004; 10: 462-478
3. Podolsky DK. Inflammatory bowel disease. N Engl J Med 2002; 347: 417-429
4. Stallmach A, Strober W, MacDonald TT, Lochs H, Zeitz M. Induction and modulation of gastrointestinal inflammation. Immunol Today 1998; 19: 438-441
5. Yu Y, Sitaraman S, Gewirtz AT. Intestinal epithelial cell regulation of mucosal inflammation. Immunol Res 2004; 29: 55-68
6. Podolsky DK, Fiocchi C. Cytokines, chemokines, growth factors, eicosanoids, and other bioactive molecules in inflammatory bowel disease. In: Kirsner JB, editor. Inflammatory Bowel Disease. 5th ed. Philadelphia: WB Saunders, 2000: 191-207
7. Swidsinski A, Ladhoff A, Pernthaler A, Swidsinski S, Loening-Baucke V, Ortner M, Weber J, Hoffmann U, Schreiber S, Dietel M, Lochs H. Mucosal flora in inflammatory bowel disease. Gastroenterology 2002; 122: 44-54
8. Loftus EV Jr. Clinical epidemiology of inflammatory bowel disease: Incidence, prevalence, and environmental influences. Gastroenterology 2004; 126: 1504-1517
9. Timmer A. Environmental influences on inflammatory bowel disease manifestations. Lessons from epidemiology. Dig Dis 2003; 21: 91-104
10. Cobrin GM, Abreu MT. Defects in mucosal immunity leading to Crohn's disease. Immunol Rev 2005; 206: 277-295
11. Shanahan F. Inflammatory bowel disease: immunodiagnostics, immunotherapeutics, and ecotherapeutics. Gastroenterology 2001; 120: 622-635
12. Fiocchi C. Inflammatory bowel disease: etiology and pathogenesis. Gastroenterology 1998; 115: 182-205
13. Xavier RJ, Podolsky DK. Unravelling the pathogenesis of inflammatory bowel disease. Nature 2007; 448: 427-434
14. Lin A, Lourenssen S, Stanzel RD, Blennerhassett MG. Selective loss of NGF-sensitive neurons following experimental colitis. Exp Neurol 2005; 191: 337-343
15. Lourenssen S, Wells RW, Blennerhassett MG. Differential responses of intrinsic and extrinsic innervation of smooth muscle cells in rat colitis. Exp Neurol 2005; 195: 497-507
16. Ohama T, Hori M, Ozaki H. Mechanism of abnormal intestinal motility in inflammatory bowel disease: how smooth muscle contraction is reduced? J Smooth Muscle Res 2007; 43: 43-54
17. Gaya DR, Russell RK, Nimmo ER, Satsangi J. New genes in inflammatory bowel disease: lessons for complex diseases? Lancet 2006; 367: 1271-1284
18. 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, Nuuez G, Cho JH. A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease. Nature 2001; 411: 603-606
19. Duerr RH, Taylor KD, Brant SR, Rioux JD, Silverberg MS, Daly MJ, Steinhart AH, Abraham C, Regueiro M, Griffiths A, Dassopoulos T, Bitton A, Yang H, Targan S, Datta LW, Kistner EO, Schumm LP, Lee AT, Gregersen PK, Barmada MM, Rotter JI, Nicolae DL, Cho JH. A genome-wide association study identifies IL23R as an inflammatory bowel disease gene. Science 2006; 314: 1461-1463
20. Hampe J, Franke A, Rosenstiel P, Till A, Teuber M, Huse K, Albrecht M, Mayr G, De La Vega FM, Briggs J, Gunther S, Prescott NJ, Onnie CM, Hasler R, Sipos B, Folsch UR, Lengauer T, Platzer M, Mathew CG, Krawczak M, Schreiber S. A genome-wide association scan of nonsynonymous SNPs identifies a susceptibility variant for Crohn disease in ATG16L1. Nat Genet 2007; 39: 207-211
21. Silverberg MS, Duerr RH, Brant SR, Bromfield G, Datta LW, Jani N, Kane SV, Rotter JI, Philip Schumm L, Hillary Steinhart A, Taylor KD, Yang H, Cho JH, Rioux JD, Daly MJ. Refined genomic localization and ethnic differences observed for the IBD5 association with Crohn's disease. Eur J Hum Genet 2007; 15: 328-335
22. Walters TD, Silverberg MS. Genetics of inflammatory bowel disease: current status and future directions. Can J Gastroenterol 2006; 20:633-639
23. Rogler G, Andus T. Cytokines in inflammatory bowel disease. World J Surg 1998; 22: 382-389
24. Papadakis KA, Targan SR. Role of cytokines in the pathogenesis of inflammatory bowel disease. Annu Rev Med 2000; 51: 289-298
25. Brown SJ, Mayer L. The immune response in inflammatory bowel disease. Am J Gastroenterol 2007; 102: 2058-2069
26. Schreiber S, Heinig T, Thiele HG, Raedler A. Immunoregulatory role of interleukin 10 in patients with inflammatory bowel disease. Gastroenterology 1995; 108: 1434-1444
27. Yen D, Cheung J, Scheerens H, Poulet F, McClanahan T, McKenzie B, Kleinschek MA, Owyang A, Mattson J, Blumenschein W, Murphy E, Sathe M, Cua DJ, Kastelein RA, Rennick D. IL-23 is essential for T cell-mediated colitis and promotes inflammation via IL-17 and IL-6. J Clin Invest 2006; 116: 1310-1316
28. Iwakura Y, Ishigame H. The IL-23/IL-17 axis in inflammation. J Clin Invest 2006; 116: 1218-1222
29. Hata K, Andoh A, Shimada M, Fujino S, Bamba S, Araki Y, Okuno T, Fujiyama Y, Bamba T. IL-17 stimulates inflammatory responses via NF-kappaB and MAP kinase pathways in human colonic myofibroblasts. Am J Physiol Gastrointest Liver Physiol 2002; 282: G1035-G1044
30. Hue S, Ahern P, Buonocore S, Kullberg MC, Cua DJ, McKenzie BS, Powrie F, Maloy KJ. Interleukin-23 drives innate and T cell-mediated intestinal inflammation. J Exp Med 2006; 203: 2473-2483
31. Kullberg MC, Jankovic D, Feng CG, Hue S, Gorelick PL, McKenzie BS, Cua DJ, Powrie F, Cheever AW, Maloy KJ, Sher A. IL-23 plays a key role in Helicobacter hepaticus-induced T cell-dependent colitis. J Exp Med 2006; 203: 2485-2494
32. Fujino S Andoh A, Bamba S, Ogawa A, Hata K, Araki Y, Bamba T, Fujiyama Y. Increased expression of interleukin 17 in inflammatory bowel disease. Gut 2003; 52: 65-70
33. Duerr RH, Taylor KD, Brant SR, Rioux JD, Silverberg MS, Daly MJ, Steinhart AH, Abraham C, Regueiro M, Griffiths A, Dassopoulos T, Bitton A, Yang H, Targan S, Datta LW, Kistner EO, Schumm LP, Lee AT, Gregersen PK, Barmada MM, Rotter JI, Nicolae DL, Cho JH. A genome-wide association study identifies IL23R as an inflammatory bowel disease gene. Science 2006; 314: 1461-1463
34. Bamias G, Martin C 3rd, Marini M, Hoang S, Mishina M, Ross WG, Sachedina MA, Friel CM, Mize J, Bickston SJ, Pizarro TT, Wei P, Cominelli F. Expression, localization, and functional activity of TL1A, a novel Th1-polarizing cytokine in inflammatory bowel disease. J Immunol 2003; 171: 4868-4874
35. Prehn JL, Mehdizadeh S, Landers CJ, Luo X, Cha SC, Wei P, Targan SR. Potential role for TL1A, the new TNF-family member and potent costimulator of IFN-gamma, in mucosal inflammation. Clin Immunol 2004; 112: 66-77
36. Yamazaki K, McGovern D, Ragoussis J, Paolucci M, Butler H, Jewell D, Cardon L, Takazoe M, Tanaka T, Ichimori T, Saito S, Sekine A, Iida A, Takahashi A, Tsunoda T, Lathrop M, Nakamura Y. Single nucleotide polymorphisms in TNFSF15 confer susceptibility to Crohn's disease. Hum Mol Genet 2005; 14: 3499-3506
37. Baumgart DC, Dignass AU. Intestinal barrier function. Curr Opin Clin Nutr Metab Care 2002; 5: 685-694
38. Gassler N, Rohr C, Schneider A, Kartenbeck J, Bach A, Obermuller N, Otto HF, Autschbach F. Inflammatory bowel disease is associated with changes of enterocytic junctions. Am J Physiol Gastrointest Liver Physiol 2001; 281: G216-G228
39. Toy LS, Yio XY, Lin A, Honig S, Mayer L. Defective expression of gp180, a novel CD8 ligand on intestinal epithelial cells, in inflammatory bowel disease. J Clin Invest 1997; 100: 2062-2071
40. Hershberg RM, Framson PE, Cho DH, Lee LY, Kovats S, Beitz J, Blum JS, Nepom GT. Intestinal epithelial cells use two distinct pathways for HLA class II antigen processing. J Clin Invest 1997; 100: 204-215
41. Hershberg RM. 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 2002; 283: G833-G839
42. Kobayashi KS, Chamaillard M, Ogura Y, Henegariu O, Inohara N, Nunez G, Flavell RA. Nod2-dependent regulation of innate and adaptive immunity in the intestinal tract. Science 2005; 307: 731-734
43. Yang SK, Eckmann L, Panja A, Kagnoff MF. Differential and regulated expression of C-X-C, C-C, and C-chemokines by human colon epithelial cells. Gastroenterology 1997; 113: 1214-1223
44. Canny G, Colgan SP. Events at the host-microbial interface of the gastrointestinal tract. I. Adaptation to a microbial world: role of epithelial bactericidal/permeability-increasing protein. Am J Physiol Gastrointest Liver Physiol 2005; 288: G593-G597
45. Neutra MR, Mantis NJ, Kraehenbuhl JP. Collaboration of epithelial cells with organized mucosal lymphoid tissues. Nat Immunol 2001; 2: 1004-1009
46. Cruickshank SM, McVay LD, Baumgart DC, Felsburg PJ, Carding SR. Colonic epithelial cell mediated suppression of CD4 T cell activation. Gut 2004; 53: 678-684
47. Cario E, Podolsky DK. Differential alteration in intestinal epithelial cell expression of toll-like receptor 3 (TLR3) and TLR4 in inflammatory bowel disease. Infect Immun 2000; 68: 7010-7017
48. Berrebi D, Maudinas R, Hugot JP, Chamaillard M, Chareyre F, De Lagausie P, Yang C, Desreumaux P, Giovannini M, Cezard JP, Zouali H, Emilie D, Peuchmaur M. Card15 gene overexpression in mononuclear and epithelial cells of the inflamed Crohn's disease colon. Gut 2003; 52: 840-846
49. Fellermann K, Stange DE, Schaeffeler E, Schmalzl H, Wehkamp J, Bevins CL, Reinisch W, Teml A, Schwab M, Lichter P, Radlwimmer B, Stange EF. A chromosome 8 gene-cluster polymorphism with low human beta-defensin 2 gene copy number predisposes to Crohn disease of the colon. Am J Hum Genet 2006; 79: 439-448
50. Torres MI, Garcia-Martin M, Fernandez MI, Nieto N, Gil A, Rios A. Experimental colitis induced by trinitrobenzenesulfonic acid: an ultrastructural and histochemical study. Dig Dis Sci 1999; 44: 2523-2529
51. Buisine MP, Desreumaux P, Leteurtre E, Copin MC, Colombel JF, Porchet N, Aubert JP. Mucin gene expression in intestinal epithelial cells in Crohn's disease. Gut 2001; 49: 544-551
52. Niess JH, Reinecker HC. Dendritic cells: the commanders-in-chief of mucosal immune defenses. Curr Opin Gastroenterol 2006; 22: 354-360
53. Hart AL, Al-Hassi HO, Rigby RJ, Bell SJ, Emmanuel AV, Knight SC, Kamm MA, Stagg AJ. Characteristics of intestinal dendritic cells in inflammatory bowel diseases. Gastroenterology 2005; 129: 50-65
54. Viney JL, Mowat AM, O'Malley JM, Williamson E, Fanger NA. Expanding dendritic cells in vivo enhances the induction of oral tolerance. J Immunol 1998; 160: 5815-5825
55. Rescigno M, Urbano M, Valzasina B, Francolini M, Rotta G, Bonasio R, Granucci F, Kraehenbuhl JP, Ricciardi-Castagnoli P. Dendritic cells express tight junction proteins and penetrate gut epithelial monolayers to sample bacteria. Nat Immunol 2001; 2: 361-367
56. Watanabe M, Takaishi H, Hosoda Y, Ezaki T, Yajima T, Inoue N, Ueno Y, Iwao Y, Ishii H, Ishikawa H. CD4+ intestinal mucosal lymphocytes in the pathogenesis of Crohn's disease. J Gastroenterol 1995; 30 Suppl 8: 73-75
57. Kraus TA, Mayer L. Oral tolerance and inflammatory bowel disease. Curr Opin Gastroenterol. 2005; 21: 692-696
58. Steinman RM, Hawiger D, Nussenzweig MC. Tolerogenic dendritic cells. Annu Rev Immunol 2003; 21: 685-711
59. Baumgart DC, Metzke D, Schmitz J, Scheffold A, Sturm A, Wiedenmann B, Dignass AU. Patients with active inflammatory bowel disease lack immature peripheral blood plasmacytoid and myeloid dendritic cells. Gut 2005; 54: 228-236
60. Mayer L. Epithelial cell antigen presentation. Curr Opin Gastroenterol 2000; 16: 531-535
61. Torres MI, Le Discorde M, Lorite P, Rios A, Gassull MA, Gil A, Maldonado J, Dausset J, Carosella ED. Expression of HLA-G in inflammatory bowel disease provides a potential way to distinguish between ulcerative colitis and Crohn's disease. Int Immunol 2004; 16: 579-583
62. Rouas-Freiss N, Goncalves RM, Menier C, Dausset J, Carosella ED. Direct evidence to support the role of HLA-G in protecting the fetus from maternal uterine natural killer cytolysis. Proc Natl Acad Sci USA 1997; 94: 11520-11525
63. Rezaie A, Parker RD, Abdollahi M. Oxidative stress and pathogenesis of inflammatory bowel disease: an epiphenomenon or the cause? Dig Dis Sci 2007; 52: 2015-2021
64. Keshavarzian A, Morgan G, Sedghi S, Gordon JH, Doria M. Role of reactive oxygen metabolites in experimental colitis. Gut 1990; 31: 786-790
65. Babbs CF. Oxygen radicals in ulcerative colitis. Free Radic Biol Med 1992; 13: 169-181
66. Grisham MB, Volkmer C, Tso F, Yamada T. Metabolism of trinitrobenzene sulfonic acid by the rat colon produces reactive oxygen species. Gastroenterology 1991; 101: 540-547
67. Nieto N, Torres MI, Fernandez MI, Giron MD, Rios A, Suarez MD, Gil A. Experimental ulcerative colitis impairs antioxidant defense system in rat intestine. Dig Dis Sci 2000; 45: 1820-1827
68. Sido B, Hack V, Hochlehnert A, Lipps H, Herfarth C, Droge W. Impairment of intestinal glutathione synthesis in patients with inflammatory bowel disease. Gut 1998; 42: 485-492
69. Lih-Brody L, Powell SR, Collier KP, Reddy GM, Cerchia R, Kahn E, Weissman GS, Katz S, Floyd RA, McKinley MJ, Fisher SE, Mullin GE. Increased oxidative stress and decreased antioxidant defenses in mucosa of inflammatory bowel disease. Dig Dis Sci 1996; 41: 2078-2086
70. Baumgart DC, Sandborn WJ. Inflammatory bowel disease: clinical aspects and established and evolving therapies. Lancet 2007; 369: 1641-1657
71. Grimble RF. Interaction between nutrients, pro-inflammatory cytokines and inflammation. Clin Sci (Lond) 1996; 91: 121-130
72. Riordan AM, Ruxton CM, Hunter JO. A review of associations between Crohn's disease and consumption of sugars. Eur J Clin Nutr 1998; 52: 229-238
73. Hunter JO. Nutritional factors in inflammatory bowel disease. Eur J Gastroenterol Hepatol 1998; 10: 235-237
74. Calder PC. Polyunsaturated fatty acids and inflammation. Prostaglandins Leukot Essent Fatty Acids 2006; 75: 197-202
75. Belluzzi A. N-3 fatty acids for the treatment of inflammatory bowel diseases. Proc Nutr Soc 2002; 61: 391-395
76. Fernandez-Banares F, Esteve-Comas M, Mane J, Navarro E, Bertran X, Cabre E, Bartoli R, Boix J, Pastor C, Gassull MA. Ghanges in mucosal fatty acid profile in inflammatorybowel disease and in experimental colitis: a common response to bowel inflammation. Clin Nutr 1997; 16: 177-183
77. Nieto N, Fernandez MI, Torres MI, Rios A, Suarez MD, Gil A. Dietary monounsaturated n-3 and n-6 long-chain polyunsaturated fatty acids affect cellular antioxidant defense system in rats with experimental ulcerative colitis induced by trinitrobenzene sulfonic acid. Dig Dis Sci 1998; 43: 2676-2687
78. Mills SC, Windsor AC, Knight SC. The potential interactions between polyunsaturated fatty acids and colonic inflammatory processes. Clin Exp Immunol 2005; 142: 216-228
79. Galvez J, Rodriguez-Cabezas ME, Zarzuelo A. Effects of dietary fiber on inflammatory bowel disease. Mol Nutr Food Res 2005; 49: 601-608
80. Segain JP, Raingeard de la Bletiere D, Bourreille A, Leray V, Gervois N, Rosales C, Ferrier L, Bonnet C, Blottiere HM, Galmiche JP. Butyrate inhibits inflammatory responses through NFkappaB inhibition: implications for Crohn's disease. Gut 2000; 47: 397-403
81. Rodriguez-Cabezas ME, Galvez J, Lorente MD, Concha A, Camuesco D, Azzouz S, Osuna A, Redondo L, Zarzuelo A. Dietary fiber down-regulates colonic tumor necrosis factor alpha and nitric oxide production in trinitrobenzenesulfonic acid-induced colitic rats. J Nutr 2002; 132: 3263-3271
82. Ewaschuk JB, Dieleman LA. Probiotics and prebiotics in chronic inflammatory bowel diseases. World J Gastroenterol 2006; 12: 5941-5950
83. Jones JL, Foxx-Orenstein AE. The role of probiotics in inflammatory bowel disease. Dig Dis Sci 2007; 52: 607-611
84. Boirivant M, Strober W. The mechanism of action of probiotics. Curr Opin Gastroenterol 2007; 23: 679-692
85. Gibson GR, Roberfroid MB. Dietary modulation of the human colonic microbiota: introducing the concept of prebiotics. J Nutr 1995; 125: 1401-1412
86. Holma R, Juvonen P, Asmawi MZ, Vapaatalo H, Korpela R. Galacto-oligosaccharides stimulate the growth of bifidobacteria but fail to attenuate inflammation in experimental colitis in rats. Scand J Gastroenterol 2002; 37: 1042-1047
87. Millard AL, Mertes PM, Ittelet D, Villard F, Jeannesson P, Bernard J. Butyrate affects differentiation, maturation and function of human monocyte-derived dendritic cells and macrophages. Clin Exp Immunol 2002; 130: 245-255
88. Middleton E, Kandaswami C. Plant flavonoid modulation of immune and inflammatory cell functions. In: Klurfeld DM. Human Nutrition: A comprehensive treatise. New York: harmacology, 1998; 57: 261-270
89. Ocete MA, Galvez J, Crespo ME, Cruz T, Gonzalez M, Torres MI, Zarzuelo A. Effects of morin on an experimental model of acute colitis in rats. Pharmacology 1998; 57: 261-270
90. Desreumaux P, Ghosh S. Review article: mode of action and delivery of 5-aminosalicylic acid - new evidence. Aliment Pharmacol Ther 2006; 24 Suppl 1: 2-9
91. Meenan J, Grool TA, Hommes DW, Dijkhuizen S, ten Kate FJ, Wood M, Whittaker M, Tytgat GN, van Deventer SJ. Lexipafant (BB-882), a platelet activating factor receptor antagonist, ameliorates mucosal inflammation in an animal model of colitis. Eur J Gastroenterol Hepatol 1996; 8: 569-573
92. Galvez J, Garrido M, Merlos M, Torres MI, Zarzuelo A. Intestinal anti-inflammatory activity of UR-12746, a novel 5-ASA conjugate, on acute and chronic experimental colitis in the rat. Br J Pharmacol 2000; 130: 1949-1959
93. Chow DK, Leong RW. The use of tacrolimus in the treatment of inflammatory bowel disease. Expert Opin Drug Saf 2007; 6: 479-485
94. Pizarro TT, Cominelli F. Cytokine therapy for Crohn's disease: advances in translational research. Annu Rev Med 2007; 58: 433-444
95. Rutgeerts P, Van Assche G, Vermeire S. Optimizing anti-TNF treatment in inflammatory bowel disease. Gastroenterology 2004; 126: 1593-1610
96. de Ridder L, Benninga MA, Taminiau JA, Hommes DW, van Deventer SJ. Infliximab use in children and adolescents with inflammatory bowel disease. J Pediatr Gastroenterol Nutr 2007; 45: 3-14
97. Van Montfrans C, Hooijberg E, Rodriguez Pena MS, De Jong EC, Spits H, Te Velde AA, Van Deventer SJ. Generation of regulatory gut-homing human T lymphocytes using ex vivo interleukin 10 gene transfer. Gastroenterology 2002; 123: 1877-1888
98. Uhlig HH, Coombes J, Mottet C, Izcue A, Thompson C, Fanger A, Tannapfel A, Fontenot JD, Ramsdell F, Powrie F. Characterization of Foxp3+CD4+CD25+ and IL-10-secreting CD4+CD25+ T cells during cure of colitis. J Immunol 2006; 177: 5852-5860
99. Plevy S, Salzberg B, Van Assche G, Regueiro M, Hommes D, Sandborn W, Hanauer S, Targan S, Mayer L, Mahadevan U, Frankel M, Lowder J. A phase I study of visilizumab, a humanized anti-CD3 monoclonal antibody, in severe steroid-refractory ulcerative colitis. Gastroenterology 2007; 133: 1414-1422
100. Oyama Y, Craig RM, Traynor AE, Quigley K, Statkute L, Halverson A, Brush M, Verda L, Kowalska B, Krosnjar N, Kletzel M, Whitington PF, Burt RK. Autologous hematopoietic stem cell transplantation in patients with refractory Crohn's disease. Gastroenterology 2005; 128: 552-563