Skip to main content
Erschienen in: Journal of Gastroenterology 1/2010

01.01.2010 | Review

Evolving paradigms in the pathogenesis of IBD

verfasst von: Lloyd Mayer

Erschienen in: Journal of Gastroenterology | Ausgabe 1/2010

Einloggen, um Zugang zu erhalten

Abstract

The pathogenesis of all immune-mediated inflammatory diseases has been carefully studied over the past several decades, but it is only recently that we have come to appreciate common pathways and genes. This is especially true for the inflammatory bowel diseases (IBD) Crohn’s disease and ulcerative colitis, where a keener appreciation of the contributions of genetics, environment, and immune response have been dissected. In fact, in many ways, IBD has become the model for studying such disorders. The complex nature of interactions is continuing to be defined, and novel therapies targeting defects in these interactions have been developed and are being tested in the clinic. The era of bench to bedside has finally matured, and cures for debilitating diseases are now in sight. This review describes our current state of knowledge of each component of IBD pathogenesis. What has evolved is a clearer picture and novel targets for therapy.
Literatur
1.
Zurück zum Zitat Ogura Y, Bonen DK, Inohara N, Nicolae DL, Chen FF, Ramos R, et al. A frameshift mutation in NOD2 associated with susceptibility to Crohn’s disease. Nature. 2001;411:603–6.CrossRefPubMed Ogura Y, Bonen DK, Inohara N, Nicolae DL, Chen FF, Ramos R, et al. A frameshift mutation in NOD2 associated with susceptibility to Crohn’s disease. Nature. 2001;411:603–6.CrossRefPubMed
2.
Zurück zum Zitat Hugot JP, Chamaillard M, Zouali H, Lesage S, Cezard JP, Belaiche J, et al. Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn’s disease. Nature. 2001;411:599–603.CrossRefPubMed Hugot JP, Chamaillard M, Zouali H, Lesage S, Cezard JP, Belaiche J, et al. Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn’s disease. Nature. 2001;411:599–603.CrossRefPubMed
3.
Zurück zum Zitat Peltekova VD, Wintle RF, Rubin LA, Amos CI, Huang Q, Gu X, et al. Functional variants of OCTN cation transporter genes are associated with Crohn disease. Nat Genet. 2004;36:471–5.CrossRefPubMed Peltekova VD, Wintle RF, Rubin LA, Amos CI, Huang Q, Gu X, et al. Functional variants of OCTN cation transporter genes are associated with Crohn disease. Nat Genet. 2004;36:471–5.CrossRefPubMed
4.
Zurück zum Zitat Brant SR, Panhuysen CI, Nicolae D, Reddy DM, Bonen DK, Karaliukas R, et al. MDR1 Ala893 polymorphism is associated with inflammatory bowel disease. Am J Hum Genet. 2003;73:1282–92.CrossRefPubMed Brant SR, Panhuysen CI, Nicolae D, Reddy DM, Bonen DK, Karaliukas R, et al. MDR1 Ala893 polymorphism is associated with inflammatory bowel disease. Am J Hum Genet. 2003;73:1282–92.CrossRefPubMed
5.
Zurück zum Zitat Hampe J, Franke A, Rosenstiel P, Till A, Teuber M, Huse K, et al. A genome-wide association scan of nonsynonymous SNPs identifies a susceptibility variant for Crohn disease in ATG16L1. Nat Genet. 2007;39:207–11.CrossRefPubMed Hampe J, Franke A, Rosenstiel P, Till A, Teuber M, Huse K, et al. A genome-wide association scan of nonsynonymous SNPs identifies a susceptibility variant for Crohn disease in ATG16L1. Nat Genet. 2007;39:207–11.CrossRefPubMed
6.
Zurück zum Zitat Rioux JD, Xavier RJ, Taylor KD, Silverberg MS, Goyette P, Huett A, et al. Genome-wide association study identifies new susceptibility loci for Crohn disease and implicates autophagy in disease pathogenesis. Nat Genet. 2007;39:596–604.CrossRefPubMed Rioux JD, Xavier RJ, Taylor KD, Silverberg MS, Goyette P, Huett A, et al. Genome-wide association study identifies new susceptibility loci for Crohn disease and implicates autophagy in disease pathogenesis. Nat Genet. 2007;39:596–604.CrossRefPubMed
7.
Zurück zum Zitat Duerr RH, Taylor KD, Brant SR, Rioux JD, Silverberg MS, Daly MJ, et al. A genome-wide association study identifies IL23R as an inflammatory bowel disease gene. Science. 2006;314:1461–3.CrossRefPubMed Duerr RH, Taylor KD, Brant SR, Rioux JD, Silverberg MS, Daly MJ, et al. A genome-wide association study identifies IL23R as an inflammatory bowel disease gene. Science. 2006;314:1461–3.CrossRefPubMed
8.
Zurück zum Zitat Podolsky DK. Lessons from genetic models of inflammatory bowel disease. Acta Gastroenterol Belg. 1997;60:163–5.PubMed Podolsky DK. Lessons from genetic models of inflammatory bowel disease. Acta Gastroenterol Belg. 1997;60:163–5.PubMed
9.
Zurück zum Zitat Strober W, Fuss I, Mannon P. The fundamental basis of inflammatory bowel disease. J Clin Invest. 2007;117:514–21.CrossRefPubMed Strober W, Fuss I, Mannon P. The fundamental basis of inflammatory bowel disease. J Clin Invest. 2007;117:514–21.CrossRefPubMed
10.
Zurück zum Zitat Braun J, Targan SR. Multiparameter analysis of immunogenetic mechanisms in clinical diagnosis and management of inflammatory bowel disease. Adv Exp Med Biol. 2006;579:209–18.CrossRefPubMed Braun J, Targan SR. Multiparameter analysis of immunogenetic mechanisms in clinical diagnosis and management of inflammatory bowel disease. Adv Exp Med Biol. 2006;579:209–18.CrossRefPubMed
11.
Zurück zum Zitat Duchmann R, Kaiser I, Hermann E, Mayet W, Ewe K, Meyer zum Buschenfelde KH. Tolerance exists towards resident intestinal flora but is broken in active inflammatory bowel disease (IBD). Clin Exp Immunol. 1995;102:448–55.PubMedCrossRef Duchmann R, Kaiser I, Hermann E, Mayet W, Ewe K, Meyer zum Buschenfelde KH. Tolerance exists towards resident intestinal flora but is broken in active inflammatory bowel disease (IBD). Clin Exp Immunol. 1995;102:448–55.PubMedCrossRef
12.
Zurück zum Zitat Mowat AM, Viney JL. The anatomical basis of intestinal immunity. Immunol Rev. 1997;156:145–66.CrossRefPubMed Mowat AM, Viney JL. The anatomical basis of intestinal immunity. Immunol Rev. 1997;156:145–66.CrossRefPubMed
13.
Zurück zum Zitat Maul J, Loddenkemper C, Mundt P, Berg E, Giese T, Stallmach A, et al. Peripheral and intestinal regulatory CD4+ CD25(high) T cells in inflammatory bowel disease. Gastroenterology. 2005;128:1868–78.CrossRefPubMed Maul J, Loddenkemper C, Mundt P, Berg E, Giese T, Stallmach A, et al. Peripheral and intestinal regulatory CD4+ CD25(high) T cells in inflammatory bowel disease. Gastroenterology. 2005;128:1868–78.CrossRefPubMed
14.
Zurück zum Zitat Mottet C, Uhlig HH, Powrie F. Cutting edge: cure of colitis by CD4+ CD25+ regulatory T cells. J Immunol. 2003;170:3939–43.PubMed Mottet C, Uhlig HH, Powrie F. Cutting edge: cure of colitis by CD4+ CD25+ regulatory T cells. J Immunol. 2003;170:3939–43.PubMed
15.
Zurück zum Zitat Brimnes J, Allez M, Dotan I, Shao L, Nakazawa A, Mayer L. Defects in CD8+ regulatory T cells in the lamina propria of patients with inflammatory bowel disease. J Immunol. 2005;174:5814–22.PubMed Brimnes J, Allez M, Dotan I, Shao L, Nakazawa A, Mayer L. Defects in CD8+ regulatory T cells in the lamina propria of patients with inflammatory bowel disease. J Immunol. 2005;174:5814–22.PubMed
16.
17.
Zurück zum Zitat Spencer DM, Veldman GM, Banerjee S, Willis J, Levine AD. Distinct inflammatory mechanisms mediate early versus late colitis in mice. Gastroenterology. 2002;122:94–105.CrossRefPubMed Spencer DM, Veldman GM, Banerjee S, Willis J, Levine AD. Distinct inflammatory mechanisms mediate early versus late colitis in mice. Gastroenterology. 2002;122:94–105.CrossRefPubMed
18.
Zurück zum Zitat Rutgeerts P, Van Assche G, Vermeire S. Optimizing anti-TNF treatment in inflammatory bowel disease. Gastroenterology. 2004;126:1593–610.CrossRefPubMed Rutgeerts P, Van Assche G, Vermeire S. Optimizing anti-TNF treatment in inflammatory bowel disease. Gastroenterology. 2004;126:1593–610.CrossRefPubMed
19.
Zurück zum Zitat Halme L, Paavola-Sakki P, Turunen U, Lappalainen M, Farkkila M, Kontula K. Family and twin studies in inflammatory bowel disease. World J Gastroenterol. 2006;12:3668–72.PubMed Halme L, Paavola-Sakki P, Turunen U, Lappalainen M, Farkkila M, Kontula K. Family and twin studies in inflammatory bowel disease. World J Gastroenterol. 2006;12:3668–72.PubMed
20.
Zurück zum Zitat Orholm M, Binder V, Sorensen TI, Rasmussen LP, Kyvik KO. Concordance of inflammatory bowel disease among Danish twins. Results of a nationwide study. Scand J Gastroenterol. 2000;35:1075–81.CrossRefPubMed Orholm M, Binder V, Sorensen TI, Rasmussen LP, Kyvik KO. Concordance of inflammatory bowel disease among Danish twins. Results of a nationwide study. Scand J Gastroenterol. 2000;35:1075–81.CrossRefPubMed
21.
Zurück zum Zitat Satsangi J, Parkes M, Jewell DP, Bell JI. Genetics of inflammatory bowel disease. Clin Sci (Lond). 1998;94:473–8. Satsangi J, Parkes M, Jewell DP, Bell JI. Genetics of inflammatory bowel disease. Clin Sci (Lond). 1998;94:473–8.
22.
Zurück zum Zitat Bernstein CN, Rawsthorne P, Cheang M, Blanchard JF. A population-based case control study of potential risk factors for IBD. Am J Gastroenterol. 2006;101:993–1002.CrossRefPubMed Bernstein CN, Rawsthorne P, Cheang M, Blanchard JF. A population-based case control study of potential risk factors for IBD. Am J Gastroenterol. 2006;101:993–1002.CrossRefPubMed
23.
Zurück zum Zitat Brant SR, Shugart YY. Inflammatory bowel disease gene hunting by linkage analysis: rationale, methodology, and present status of the field. Inflamm Bowel Dis. 2004;10:300–11.CrossRefPubMed Brant SR, Shugart YY. Inflammatory bowel disease gene hunting by linkage analysis: rationale, methodology, and present status of the field. Inflamm Bowel Dis. 2004;10:300–11.CrossRefPubMed
24.
Zurück zum Zitat Esters N, Pierik M, van Steen K, Vermeire S, Claessens G, Joossens S, et al. Transmission of CARD15 (NOD2) variants within families of patients with inflammatory bowel disease. Am J Gastroenterol. 2004;99:299–305.CrossRefPubMed Esters N, Pierik M, van Steen K, Vermeire S, Claessens G, Joossens S, et al. Transmission of CARD15 (NOD2) variants within families of patients with inflammatory bowel disease. Am J Gastroenterol. 2004;99:299–305.CrossRefPubMed
25.
Zurück zum Zitat Weiss B, Shamir R, Bujanover Y, Waterman M, Hartman C, Fradkin A, et al. NOD2/CARD15 mutation analysis and genotype-phenotype correlation in Jewish pediatric patients compared with adults with Crohn’s disease. J Pediatr. 2004;145:208–12.CrossRefPubMed Weiss B, Shamir R, Bujanover Y, Waterman M, Hartman C, Fradkin A, et al. NOD2/CARD15 mutation analysis and genotype-phenotype correlation in Jewish pediatric patients compared with adults with Crohn’s disease. J Pediatr. 2004;145:208–12.CrossRefPubMed
26.
Zurück zum Zitat Abreu MT, Taylor KD, Lin YC, Hang T, Gaiennie J, Landers CJ, et al. Mutations in NOD2 are associated with fibrostenosing disease in patients with Crohn’s disease. Gastroenterology. 2002;123:679–88.CrossRefPubMed Abreu MT, Taylor KD, Lin YC, Hang T, Gaiennie J, Landers CJ, et al. Mutations in NOD2 are associated with fibrostenosing disease in patients with Crohn’s disease. Gastroenterology. 2002;123:679–88.CrossRefPubMed
27.
Zurück zum Zitat Halfvarson J, Bodin L, Tysk C, Lindberg E, Jarnerot G. Inflammatory bowel disease in a Swedish twin cohort: a long-term follow-up of concordance and clinical characteristics. Gastroenterology. 2003;124:1767–73.CrossRefPubMed Halfvarson J, Bodin L, Tysk C, Lindberg E, Jarnerot G. Inflammatory bowel disease in a Swedish twin cohort: a long-term follow-up of concordance and clinical characteristics. Gastroenterology. 2003;124:1767–73.CrossRefPubMed
28.
Zurück zum Zitat Halfvarson J, Jess T, Bodin L, Jarnerot G, Munkholm P, Binder V, et al. Longitudinal concordance for clinical characteristics in a Swedish–Danish twin population with inflammatory bowel disease. Inflamm Bowel Dis. 2007;13:1536–44.CrossRefPubMed Halfvarson J, Jess T, Bodin L, Jarnerot G, Munkholm P, Binder V, et al. Longitudinal concordance for clinical characteristics in a Swedish–Danish twin population with inflammatory bowel disease. Inflamm Bowel Dis. 2007;13:1536–44.CrossRefPubMed
29.
Zurück zum Zitat Chiba M, Fukushima T, Horie Y, Iizuka M, Masamune O. No Mycobacterium paratuberculosis detected in intestinal tissue, including Peyer’s patches and lymph follicles, of Crohn’s disease. J Gastroenterol. 1998;33:482–7.CrossRefPubMed Chiba M, Fukushima T, Horie Y, Iizuka M, Masamune O. No Mycobacterium paratuberculosis detected in intestinal tissue, including Peyer’s patches and lymph follicles, of Crohn’s disease. J Gastroenterol. 1998;33:482–7.CrossRefPubMed
30.
Zurück zum Zitat Drossman DA. Presidential address: gastrointestinal illness and the biopsychosocial model. Psychosom Med. 1998;60:258–67.PubMed Drossman DA. Presidential address: gastrointestinal illness and the biopsychosocial model. Psychosom Med. 1998;60:258–67.PubMed
31.
Zurück zum Zitat Medzhitov R, Janeway C Jr. Innate immune recognition: mechanisms and pathways. Immunol Rev. 2000;173:89–97.CrossRefPubMed Medzhitov R, Janeway C Jr. Innate immune recognition: mechanisms and pathways. Immunol Rev. 2000;173:89–97.CrossRefPubMed
32.
Zurück zum Zitat Janeway CA Jr, Bottomly K. Signals and signs for lymphocyte responses. Cell. 1994;76:275–85.CrossRefPubMed Janeway CA Jr, Bottomly K. Signals and signs for lymphocyte responses. Cell. 1994;76:275–85.CrossRefPubMed
33.
Zurück zum Zitat Medzhitov R, Janeway CA Jr. Innate immune recognition and control of adaptive immune responses. Semin Immunol. 1998;10:351–3.CrossRefPubMed Medzhitov R, Janeway CA Jr. Innate immune recognition and control of adaptive immune responses. Semin Immunol. 1998;10:351–3.CrossRefPubMed
34.
Zurück zum Zitat Huang JS, Noack D, Rae J, Ellis BA, Newbury R, Pong AL, et al. Chronic granulomatous disease caused by a deficiency in p47(phox) mimicking Crohn’s disease. Clin Gastroenterol Hepatol. 2004;2:690–5.CrossRefPubMed Huang JS, Noack D, Rae J, Ellis BA, Newbury R, Pong AL, et al. Chronic granulomatous disease caused by a deficiency in p47(phox) mimicking Crohn’s disease. Clin Gastroenterol Hepatol. 2004;2:690–5.CrossRefPubMed
35.
Zurück zum Zitat Schinella RA, Greco MA, Cobert BL, Denmark LW, Cox RP. Hermansky–Pudlak syndrome with granulomatous colitis. Ann Int Med. 1980;92:20–3.PubMed Schinella RA, Greco MA, Cobert BL, Denmark LW, Cox RP. Hermansky–Pudlak syndrome with granulomatous colitis. Ann Int Med. 1980;92:20–3.PubMed
36.
Zurück zum Zitat Dieckgraefe BK, Korzenik JR. Treatment of active Crohn’s disease with recombinant human granulocyte–macrophage colony-stimulating factor. Lancet. 2002;360:1478–80.CrossRefPubMed Dieckgraefe BK, Korzenik JR. Treatment of active Crohn’s disease with recombinant human granulocyte–macrophage colony-stimulating factor. Lancet. 2002;360:1478–80.CrossRefPubMed
37.
Zurück zum Zitat Kugathasan S, Saubermann LJ, Smith L, Kou D, Itoh J, Binion DG, et al. Mucosal T-cell immunoregulation varies in early and late inflammatory bowel disease. Gut. 2007;56:1696–705.CrossRefPubMed Kugathasan S, Saubermann LJ, Smith L, Kou D, Itoh J, Binion DG, et al. Mucosal T-cell immunoregulation varies in early and late inflammatory bowel disease. Gut. 2007;56:1696–705.CrossRefPubMed
38.
Zurück zum Zitat Brown SJ, Mayer L. The immune response in inflammatory bowel disease. Am J Gastroenterol. 2007;102:2058–69.CrossRefPubMed Brown SJ, Mayer L. The immune response in inflammatory bowel disease. Am J Gastroenterol. 2007;102:2058–69.CrossRefPubMed
39.
Zurück zum Zitat Fuss IJ, Heller F, Boirivant M, Leon F, Yoshida M, Fichtner-Feigl S, et al. Nonclassical CD1d-restricted NK T cells that produce IL-13 characterize an atypical Th2 response in ulcerative colitis. J Clin Invest. 2004;113:1490–7.PubMed Fuss IJ, Heller F, Boirivant M, Leon F, Yoshida M, Fichtner-Feigl S, et al. Nonclassical CD1d-restricted NK T cells that produce IL-13 characterize an atypical Th2 response in ulcerative colitis. J Clin Invest. 2004;113:1490–7.PubMed
40.
Zurück zum Zitat Fuss IJ, Neurath M, Boirivant M, Klein JS, de la Motte C, Strong SA, et al. Disparate CD4+ lamina propria (LP) lymphokine secretion profiles in inflammatory bowel disease. Crohn’s disease LP cells manifest increased secretion of IFN-gamma, whereas ulcerative colitis LP cells manifest increased secretion of IL-5. J Immunol. 1996;157:1261–70.PubMed Fuss IJ, Neurath M, Boirivant M, Klein JS, de la Motte C, Strong SA, et al. Disparate CD4+ lamina propria (LP) lymphokine secretion profiles in inflammatory bowel disease. Crohn’s disease LP cells manifest increased secretion of IFN-gamma, whereas ulcerative colitis LP cells manifest increased secretion of IL-5. J Immunol. 1996;157:1261–70.PubMed
41.
Zurück zum Zitat van Assche G. Emerging drugs to treat Crohn’s disease. Expert Opin Emerg Drugs. 2007;12:49–59.CrossRefPubMed van Assche G. Emerging drugs to treat Crohn’s disease. Expert Opin Emerg Drugs. 2007;12:49–59.CrossRefPubMed
42.
Zurück zum Zitat Kobayashi K, Kaneda K, Kasama T. Immunopathogenesis of delayed-type hypersensitivity. Microsc Res Tech. 2001;53:241–5.CrossRefPubMed Kobayashi K, Kaneda K, Kasama T. Immunopathogenesis of delayed-type hypersensitivity. Microsc Res Tech. 2001;53:241–5.CrossRefPubMed
43.
44.
Zurück zum Zitat Berlin C, Berg EL, Briskin MJ, Andrew DP, Kilshaw PJ, Holzmann B, et al. Alpha 4 beta 7 integrin mediates lymphocyte binding to the mucosal vascular addressin MAdCAM-1. Cell. 1993;74:185–95.CrossRefPubMed Berlin C, Berg EL, Briskin MJ, Andrew DP, Kilshaw PJ, Holzmann B, et al. Alpha 4 beta 7 integrin mediates lymphocyte binding to the mucosal vascular addressin MAdCAM-1. Cell. 1993;74:185–95.CrossRefPubMed
45.
Zurück zum Zitat MacDonald TT, Bajaj-Elliott M, Pender SL. T cells orchestrate intestinal mucosal shape and integrity. Immunol Today. 1999;20:505–10.CrossRefPubMed MacDonald TT, Bajaj-Elliott M, Pender SL. T cells orchestrate intestinal mucosal shape and integrity. Immunol Today. 1999;20:505–10.CrossRefPubMed
46.
Zurück zum Zitat Alber G, Al-Robaiy S, Kleinschek M, Knauer J, Krumbholz P, Richter J, Schoeneberger S, Schuetze N, Schulz S, Toepfer K, Voigtlaender R, Lehmann J, Mueller U. Induction of immunity and inflammation by interleukin-12 family members. Ernst Schering Res Found Workshop 2006:107–27. Alber G, Al-Robaiy S, Kleinschek M, Knauer J, Krumbholz P, Richter J, Schoeneberger S, Schuetze N, Schulz S, Toepfer K, Voigtlaender R, Lehmann J, Mueller U. Induction of immunity and inflammation by interleukin-12 family members. Ernst Schering Res Found Workshop 2006:107–27.
47.
Zurück zum Zitat Hunter CA. New IL-12-family members: IL-23 and IL-27, cytokines with divergent functions. Nat Rev Immunol. 2005;5:521–31.CrossRefPubMed Hunter CA. New IL-12-family members: IL-23 and IL-27, cytokines with divergent functions. Nat Rev Immunol. 2005;5:521–31.CrossRefPubMed
48.
Zurück zum Zitat Elloumi-Zghal H, Barbouche MR, Chemli J, Bejaoui M, Harbi A, Snoussi N, et al. Clinical and genetic heterogeneity of inherited autosomal recessive susceptibility to disseminated Mycobacterium bovis bacille calmette-guerin infection. J Infect Dis. 2002;185:1468–75.CrossRefPubMed Elloumi-Zghal H, Barbouche MR, Chemli J, Bejaoui M, Harbi A, Snoussi N, et al. Clinical and genetic heterogeneity of inherited autosomal recessive susceptibility to disseminated Mycobacterium bovis bacille calmette-guerin infection. J Infect Dis. 2002;185:1468–75.CrossRefPubMed
49.
Zurück zum Zitat Sakai T, Matsuoka M, Aoki M, Nosaka K, Mitsuya H. Missense mutation of the interleukin-12 receptor beta1 chain-encoding gene is associated with impaired immunity against Mycobacterium avium complex infection. Blood. 2001;97:2688–94.CrossRefPubMed Sakai T, Matsuoka M, Aoki M, Nosaka K, Mitsuya H. Missense mutation of the interleukin-12 receptor beta1 chain-encoding gene is associated with impaired immunity against Mycobacterium avium complex infection. Blood. 2001;97:2688–94.CrossRefPubMed
50.
Zurück zum Zitat Weaver CT, Hatton RD, Mangan PR, Harrington LE. IL-17 family cytokines and the expanding diversity of effector T cell lineages. Annu Rev Immunol. 2007;25:821–52.CrossRefPubMed Weaver CT, Hatton RD, Mangan PR, Harrington LE. IL-17 family cytokines and the expanding diversity of effector T cell lineages. Annu Rev Immunol. 2007;25:821–52.CrossRefPubMed
51.
Zurück zum Zitat Zhou L, Ivanov II, Spolski R, Min R, Shenderov K, Egawa T, et al. IL-6 programs T(H)-17 cell differentiation by promoting sequential engagement of the IL-21 and IL-23 pathways. Nat Immunol. 2007;8:967–74.CrossRefPubMed Zhou L, Ivanov II, Spolski R, Min R, Shenderov K, Egawa T, et al. IL-6 programs T(H)-17 cell differentiation by promoting sequential engagement of the IL-21 and IL-23 pathways. Nat Immunol. 2007;8:967–74.CrossRefPubMed
52.
Zurück zum Zitat Fujino S, Andoh A, Bamba S, Ogawa A, Hata K, Araki Y, et al. Increased expression of interleukin 17 in inflammatory bowel disease. Gut. 2003;52:65–70.CrossRefPubMed Fujino S, Andoh A, Bamba S, Ogawa A, Hata K, Araki Y, et al. Increased expression of interleukin 17 in inflammatory bowel disease. Gut. 2003;52:65–70.CrossRefPubMed
53.
Zurück zum Zitat Fuss IJ, Becker C, Yang Z, Groden C, Hornung RL, Heller F, 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. 2006;12:9–15.CrossRefPubMed Fuss IJ, Becker C, Yang Z, Groden C, Hornung RL, Heller F, 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. 2006;12:9–15.CrossRefPubMed
54.
Zurück zum Zitat Umetsu DT, DeKruyff RH. Th1 and Th2 CD4+ cells in the pathogenesis of allergic diseases. Proc Soc Exp Biol Med. 1997;215:11–20.PubMed Umetsu DT, DeKruyff RH. Th1 and Th2 CD4+ cells in the pathogenesis of allergic diseases. Proc Soc Exp Biol Med. 1997;215:11–20.PubMed
55.
Zurück zum Zitat Bouma G, Strober W. The immunological and genetic basis of inflammatory bowel disease. Nat Rev Immunol. 2003;3:521–33.CrossRefPubMed Bouma G, Strober W. The immunological and genetic basis of inflammatory bowel disease. Nat Rev Immunol. 2003;3:521–33.CrossRefPubMed
56.
Zurück zum Zitat Heller F, Florian P, Bojarski C, Richter J, Christ M, Hillenbrand B, et al. Interleukin-13 is the key effector Th2 cytokine in ulcerative colitis that affects epithelial tight junctions, apoptosis, and cell restitution. Gastroenterology. 2005;129:550–64.PubMed Heller F, Florian P, Bojarski C, Richter J, Christ M, Hillenbrand B, et al. Interleukin-13 is the key effector Th2 cytokine in ulcerative colitis that affects epithelial tight junctions, apoptosis, and cell restitution. Gastroenterology. 2005;129:550–64.PubMed
57.
Zurück zum Zitat Rutgeerts P, Sandborn WJ, Feagan BG, Reinisch W, Olson A, Johanns J, et al. Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2005;353:2462–76.CrossRefPubMed Rutgeerts P, Sandborn WJ, Feagan BG, Reinisch W, Olson A, Johanns J, et al. Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2005;353:2462–76.CrossRefPubMed
58.
Zurück zum Zitat Annunziato F, Cosmi L, Santarlasci V, Maggi L, Liotta F, Mazzinghi B, et al. Phenotypic and functional features of human Th17 cells. J Exp Med. 2007;204:1849–61.CrossRefPubMed Annunziato F, Cosmi L, Santarlasci V, Maggi L, Liotta F, Mazzinghi B, et al. Phenotypic and functional features of human Th17 cells. J Exp Med. 2007;204:1849–61.CrossRefPubMed
59.
Zurück zum Zitat Denning TL, Qi H, Konig R, Scott KG, Naganuma M, Ernst PB. CD4+ Th cells resembling regulatory T cells that inhibit chronic colitis differentiate in the absence of interactions between CD4 and class II MHC. J Immunol. 2003;171:2279–86.PubMed Denning TL, Qi H, Konig R, Scott KG, Naganuma M, Ernst PB. CD4+ Th cells resembling regulatory T cells that inhibit chronic colitis differentiate in the absence of interactions between CD4 and class II MHC. J Immunol. 2003;171:2279–86.PubMed
60.
Zurück zum Zitat Hosoe N, Miura S, Watanabe C, Tsuzuki Y, Hokari R, Oyama T, et al. Demonstration of functional role of TECK/CCL25 in T lymphocyte–endothelium interaction in inflamed and uninflamed intestinal mucosa. Am J Physiol Gastrointest Liver Physiol. 2004;286:G458–66.CrossRefPubMed Hosoe N, Miura S, Watanabe C, Tsuzuki Y, Hokari R, Oyama T, et al. Demonstration of functional role of TECK/CCL25 in T lymphocyte–endothelium interaction in inflamed and uninflamed intestinal mucosa. Am J Physiol Gastrointest Liver Physiol. 2004;286:G458–66.CrossRefPubMed
61.
Zurück zum Zitat Lu B, Humbles A, Bota D, Gerard C, Moser B, Soler D, et al. Structure and function of the murine chemokine receptor CXCR3. Eur J Immunol. 1999;29:3804–12.CrossRefPubMed Lu B, Humbles A, Bota D, Gerard C, Moser B, Soler D, et al. Structure and function of the murine chemokine receptor CXCR3. Eur J Immunol. 1999;29:3804–12.CrossRefPubMed
62.
Zurück zum Zitat Neurath MF, Finotto S, Fuss I, Boirivant M, Galle PR, Strober W. Regulation of T-cell apoptosis in inflammatory bowel disease: to die or not to die, that is the mucosal question. Trends Immunol. 2001;22:21–6.CrossRefPubMed Neurath MF, Finotto S, Fuss I, Boirivant M, Galle PR, Strober W. Regulation of T-cell apoptosis in inflammatory bowel disease: to die or not to die, that is the mucosal question. Trends Immunol. 2001;22:21–6.CrossRefPubMed
63.
Zurück zum Zitat Ghosh S, Goldin E, Gordon FH, Malchow HA, Rask-Madsen J, Rutgeerts P, et al. Natalizumab for active Crohn’s disease. N Engl J Med. 2003;348:24–32.CrossRefPubMed Ghosh S, Goldin E, Gordon FH, Malchow HA, Rask-Madsen J, Rutgeerts P, et al. Natalizumab for active Crohn’s disease. N Engl J Med. 2003;348:24–32.CrossRefPubMed
64.
Zurück zum Zitat Stephens GL, Shevach EM. Foxp3+ regulatory T cells: selfishness under scrutiny. Immunity. 2007;27:417–9.CrossRefPubMed Stephens GL, Shevach EM. Foxp3+ regulatory T cells: selfishness under scrutiny. Immunity. 2007;27:417–9.CrossRefPubMed
65.
Zurück zum Zitat Zheng Y, Rudensky AY. Foxp3 in control of the regulatory T cell lineage. Nat Immunol. 2007;8:457–62.CrossRefPubMed Zheng Y, Rudensky AY. Foxp3 in control of the regulatory T cell lineage. Nat Immunol. 2007;8:457–62.CrossRefPubMed
66.
Zurück zum Zitat Cong Y, Weaver CT, Lazenby A, Elson CO. Bacterial-reactive T regulatory cells inhibit pathogenic immune responses to the enteric flora. J Immunol. 2002;169:6112–9.PubMed Cong Y, Weaver CT, Lazenby A, Elson CO. Bacterial-reactive T regulatory cells inhibit pathogenic immune responses to the enteric flora. J Immunol. 2002;169:6112–9.PubMed
67.
Zurück zum Zitat Rennick DM, Fort MM, Davidson NJ. Studies with IL-10-/- mice: an overview. J Leukoc Biol. 1997;61:389–96.PubMed Rennick DM, Fort MM, Davidson NJ. Studies with IL-10-/- mice: an overview. J Leukoc Biol. 1997;61:389–96.PubMed
68.
Zurück zum Zitat Coffman RL, Lebman DA, Shrader B. Transforming growth factor beta specifically enhances IgA production by lipopolysaccharide-stimulated murine B lymphocytes. J Exp Med. 1989;170:1039–44.CrossRefPubMed Coffman RL, Lebman DA, Shrader B. Transforming growth factor beta specifically enhances IgA production by lipopolysaccharide-stimulated murine B lymphocytes. J Exp Med. 1989;170:1039–44.CrossRefPubMed
69.
Zurück zum Zitat Ruemmele FM, Brousse N, Goulet O. Autoimmune enteropathy: molecular concepts. Curr Opin Gastroenterol. 2004;20:587–91.CrossRefPubMed Ruemmele FM, Brousse N, Goulet O. Autoimmune enteropathy: molecular concepts. Curr Opin Gastroenterol. 2004;20:587–91.CrossRefPubMed
70.
Zurück zum Zitat Ochs HD, Gambineri E, Torgerson TR. IPEX, FOXP3 and regulatory T-cells: a model for autoimmunity. Immunol Res. 2007;38:112–21.CrossRefPubMed Ochs HD, Gambineri E, Torgerson TR. IPEX, FOXP3 and regulatory T-cells: a model for autoimmunity. Immunol Res. 2007;38:112–21.CrossRefPubMed
71.
Zurück zum Zitat Allez M, Brimnes J, Dotan I, Mayer L. Expansion of CD8+ T cells with regulatory function after interaction with intestinal epithelial cells. Gastroenterology. 2002;123:1516–26.CrossRefPubMed Allez M, Brimnes J, Dotan I, Mayer L. Expansion of CD8+ T cells with regulatory function after interaction with intestinal epithelial cells. Gastroenterology. 2002;123:1516–26.CrossRefPubMed
72.
Zurück zum Zitat Kraus TA, Toy L, Chan L, Childs J, Cheifetz A, Mayer L. Failure to induce oral tolerance in Crohn’s and ulcerative colitis patients: possible genetic risk. Ann N Y Acad Sci. 2004;1029:225–38.CrossRefPubMed Kraus TA, Toy L, Chan L, Childs J, Cheifetz A, Mayer L. Failure to induce oral tolerance in Crohn’s and ulcerative colitis patients: possible genetic risk. Ann N Y Acad Sci. 2004;1029:225–38.CrossRefPubMed
73.
Zurück zum Zitat Kraus TA, Toy L, Chan L, Childs J, Mayer L. Failure to induce oral tolerance to a soluble protein in patients with inflammatory bowel disease. Gastroenterology. 2004;126:1771–8.CrossRefPubMed Kraus TA, Toy L, Chan L, Childs J, Mayer L. Failure to induce oral tolerance to a soluble protein in patients with inflammatory bowel disease. Gastroenterology. 2004;126:1771–8.CrossRefPubMed
Metadaten
Titel
Evolving paradigms in the pathogenesis of IBD
verfasst von
Lloyd Mayer
Publikationsdatum
01.01.2010
Verlag
Springer Japan
Erschienen in
Journal of Gastroenterology / Ausgabe 1/2010
Print ISSN: 0944-1174
Elektronische ISSN: 1435-5922
DOI
https://doi.org/10.1007/s00535-009-0138-3

Weitere Artikel der Ausgabe 1/2010

Journal of Gastroenterology 1/2010 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Notfall-TEP der Hüfte ist auch bei 90-Jährigen machbar

26.04.2024 Hüft-TEP Nachrichten

Ob bei einer Notfalloperation nach Schenkelhalsfraktur eine Hemiarthroplastik oder eine totale Endoprothese (TEP) eingebaut wird, sollte nicht allein vom Alter der Patientinnen und Patienten abhängen. Auch über 90-Jährige können von der TEP profitieren.

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Bei schweren Reaktionen auf Insektenstiche empfiehlt sich eine spezifische Immuntherapie

Insektenstiche sind bei Erwachsenen die häufigsten Auslöser einer Anaphylaxie. Einen wirksamen Schutz vor schweren anaphylaktischen Reaktionen bietet die allergenspezifische Immuntherapie. Jedoch kommt sie noch viel zu selten zum Einsatz.

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

25.04.2024 Hypertonie Nachrichten

Beginnen ältere Männer im Pflegeheim eine Antihypertensiva-Therapie, dann ist die Frakturrate in den folgenden 30 Tagen mehr als verdoppelt. Besonders häufig stürzen Demenzkranke und Männer, die erstmals Blutdrucksenker nehmen. Dafür spricht eine Analyse unter US-Veteranen.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.