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Abdominal Radiology
Erschienen in: Abdominal Radiology 6/2012

01.12.2012

Insight into Crohn’s disease pathomorphology

verfasst von: Jonas Mudter, Markus F. Neurath

Erschienen in: Abdominal Radiology | Ausgabe 6/2012

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Abstract

Crohn’s disease (CD) belongs together with ulcerative colitis to the two major forms of inflammatory bowel diseases (IBD). Although its etiology remains poorly understood, several genetic and immune factors and cells (especially T cells) have been shown to be involved in the pathogenesis of IBD. Among these factors, proinflammatory T cells and their secreted cytokines seem to be the main effectors in induction and perpetuation of the intestinal inflammation. Beside the local inflammatory effect, there is a very clear defined mechanism where T cells and inflammatory complexes migrate and induce extraintestinal manifestation and complications. This article reviews current knowledge of the pathomorphology of mucosal inflammation in CD focusing especially on the immune mechanisms of T-cell homing, extraintestinal manifestations and fibrogenesis.
Literatur
1.
Neurath MF, Finotto S (2006) The many roads to inflammatory bowel diseases. Immunity 25:189–191PubMedCrossRef
2.
Neurath MF, Finotto S, Glimcher LH (2002) The role of Th1/Th2 polarization in mucosal immunity. Nat Med 8:567–573PubMedCrossRef
3.
Kaser A, Zeissig S, Blumberg RS (2010) Inflammatory bowel disease. Annu Rev Immunol 28:573–621PubMedCrossRef
4.
5.
Neurath MF (2000) Immunotherapy of inflammatory bowel diseases: current concepts and future perspectives. Arch Immunol Ther Exp (Warsz) 48:81–84
6.
Bouma G, Strober W (2003) The immunological and genetic basis of inflammatory bowel disease. Nat Rev Immunol 3:521–533PubMedCrossRef
7.
Colombel JF, Watson AJ, Neurath MF (2008) The 10 remaining mysteries of inflammatory bowel disease. Gut 57:429–433PubMedCrossRef
8.
Fuss IJ, Neurath M, Boirivant M, et al. (1996) 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 157:1261–1270PubMed
9.
Heller F, Florian P, Bojarski C, et al. (2005) Interleukin-13 is the key effector Th2 cytokine in ulcerative colitis that affects epithelial tight junctions, apoptosis, and cell restitution. Gastroenterology 129:550–564PubMed
10.
11.
Duerr RH, Taylor KD, Brant SR, et al. (2006) A genome-wide association study identifies IL23R as an inflammatory bowel disease gene. Science 314:1461–1463PubMedCrossRef
12.
Mudter J, Neurath MF (2007) Il-6 signaling in inflammatory bowel disease: pathophysiological role and clinical relevance. Inflamm Bowel Dis 13:1016–1023PubMedCrossRef
13.
Harrington LE, Hatton RD, Mangan PR, et al. (2005) Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nat Immunol 6:1123–1132PubMedCrossRef
14.
Annunziato F, Cosmi L, Santarlasci V, et al. (2007) Phenotypic and functional features of human Th17 cells. J Exp Med 204:1849–1861PubMedCrossRef
15.
Cosmi L, De Palma R, Santarlasci V, et al. (2008) Human interleukin 17-producing cells originate from a CD161+ CD4+ T cell precursor. J Exp Med 205:1903–1916PubMedCrossRef
16.
Sakuraba A, Sato T, Kamada N, et al. (2009) Th1/Th17 immune response is induced by mesenteric lymph node dendritic cells in Crohn’s disease. Gastroenterology 137:1736–1745PubMedCrossRef
17.
Hundorfean G, Neurath MF, Mudter J (2012) Functional relevance of T helper 17 (Th17) cells and the IL-17 cytokine family in inflammatory bowel disease. Inflamm Bowel Dis 18:180–186PubMedCrossRef
18.
Luster AD, Alon R, von Andrian UH (2005) Immune cell migration in inflammation: present and future therapeutic targets. Nat Immunol 6:1182–1190PubMedCrossRef
19.
Barrett JC, Hansoul S, Nicolae DL, et al. (2008) Genome-wide association defines more than 30 distinct susceptibility loci for Crohn’s disease. Nat Genet 40:955–962PubMedCrossRef
20.
Parkes M, Barrett JC, Prescott NJ, et al. (2007) Sequence variants in the autophagy gene IRGM and multiple other replicating loci contribute to Crohn’s disease susceptibility. Nat Genet 39:830–832PubMedCrossRef
21.
Mora JR, Bono MR, Manjunath N, et al. (2003) Selective imprinting of gut-homing T cells by Peyer’s patch dendritic cells. Nature 424:88–93PubMedCrossRef
22.
23.
Mavigner M, Cazabat M, Dubois M, et al. (2012) Altered CD4+ T cell homing to the gut impairs mucosal immune reconstitution in treated HIV-infected individuals. J Clin Invest 122:62–69PubMedCrossRef
24.
Rivera-Nieves J, Burcin TL, Olson TS, et al. (2006) Critical role of endothelial P-selectin glycoprotein ligand 1 in chronic murine ileitis. J Exp Med 203:907–917PubMedCrossRef
25.
Kosiewicz MM, Nast CC, Krishnan A, et al. (2001) Th1-type responses mediate spontaneous ileitis in a novel murine model of Crohn’s disease. J Clin Invest 107:695–702PubMedCrossRef
26.
Kuhl AA, Kakirman H, Janotta M, et al. (2007) Aggravation of different types of experimental colitis by depletion or adhesion blockade of neutrophils. Gastroenterology 133:1882–1892PubMedCrossRef
27.
Kwon JH, Keates S, Bassani L, Mayer LF, Keates AC (2002) Colonic epithelial cells are a major site of macrophage inflammatory protein 3alpha (MIP-3alpha) production in normal colon and inflammatory bowel disease. Gut 51:818–826PubMedCrossRef
28.
Kaser A, Ludwiczek O, Holzmann S, et al. (2004) Increased expression of CCL20 in human inflammatory bowel disease. J Clin Immunol 24:74–85PubMedCrossRef
29.
Acosta-Rodriguez EV, Rivino L, Geginat J, et al. (2007) Surface phenotype and antigenic specificity of human interleukin 17-producing T helper memory cells. Nat Immunol 8:639–646PubMedCrossRef
30.
Wang C, Kang SG, Lee J, Sun Z, Kim CH (2009) The roles of CCR6 in migration of Th17 cells and regulation of effector T-cell balance in the gut. Mucosal Immunol 2:173–183PubMedCrossRef
31.
Glatigny S, Duhen R, Oukka M, Bettelli E (2011) Cutting Edge: Loss of alpha4 Integrin Expression Differentially Affects the Homing of Th1 and Th17 Cells. J Immunol 187:6176–6179PubMedCrossRef
32.
Bouskra D, Brezillon C, Berard M, et al. (2008) Lymphoid tissue genesis induced by commensals through NOD1 regulates intestinal homeostasis. Nature 456:507–510PubMedCrossRef
33.
Danese S, Semeraro S, Papa A, et al. (2005) Extraintestinal manifestations in inflammatory bowel disease. World J Gastroenterol 11:7227–7236PubMed
34.
Veloso FT, Carvalho J, Magro F (1996) Immune-related systemic manifestations of inflammatory bowel disease. A prospective study of 792 patients. J Clin Gastroenterol 23:29–34PubMedCrossRef
35.
Van den Bosch F, Kruithof E, De Vos M, De Keyser F, Mielants H (2000) Crohn’s disease associated with spondyloarthropathy: effect of TNF-alpha blockade with infliximab on articular symptoms. Lancet 356:1821–1822PubMedCrossRef
36.
Herfarth H, Obermeier F, Andus T, et al. (2002) Improvement of arthritis and arthralgia after treatment with infliximab (Remicade) in a German prospective, open-label, multicenter trial in refractory Crohn’s disease. Am J Gastroenterol 97:2688–2690PubMedCrossRef
37.
Aerts NE, De Knop KJ, Leysen J, et al. (2010) Increased IL-17 production by peripheral T helper cells after tumour necrosis factor blockade in rheumatoid arthritis is accompanied by inhibition of migration-associated chemokine receptor expression. Rheumatology (Oxford) 49:2264–2272CrossRef
38.
Schwartz DA, Loftus EV Jr, Tremaine WJ, et al. (2002) The natural history of fistulizing Crohn’s disease in Olmsted County, Minnesota. Gastroenterology 122:875–880PubMedCrossRef
39.
Podolsky DK (2002) The current future understanding of inflammatory bowel disease. Best Pract Res Clin Gastroenterol 16:933–943PubMedCrossRef
40.
Menachem Y, Gotsman I (2004) Clinical manifestations of pyoderma gangrenosum associated with inflammatory bowel disease. Isr Med Assoc J 6:88–90PubMed
41.
Loftus EV Jr, Sandborn WJ, Tremaine WJ, et al. (1996) Risk of colorectal neoplasia in patients with primary sclerosing cholangitis. Gastroenterology 110:432–440PubMedCrossRef
42.
Rieder F, Fiocchi C (2009) Intestinal fibrosis in IBD—a dynamic, multifactorial process. Nat Rev Gastroenterol Hepatol 6:228–235PubMedCrossRef
43.
Pucilowska JB, Williams KL, Lund PK (2000) Fibrogenesis. IV. Fibrosis and inflammatory bowel disease: cellular mediators and animal models. Am J Physiol Gastrointest Liver Physiol 279:G653–G659PubMed
44.
Becker JM (1999) Surgical therapy for ulcerative colitis and Crohn’s disease. Gastroenterol Clin North Am 28:371–390, viii-ix
45.
Powell DW, Mifflin RC, Valentich JD, et al. (1999) Myofibroblasts. I. Paracrine cells important in health and disease. Am J Physiol 277:C1–C9PubMed
46.
Lawrance IC, Maxwell L, Doe W (2001) Altered response of intestinal mucosal fibroblasts to profibrogenic cytokines in inflammatory bowel disease. Inflamm Bowel Dis 7:226–236PubMedCrossRef
47.
Simmons JG, Pucilowska JB, Keku TO, Lund PK (2002) IGF-I and TGF-beta1 have distinct effects on phenotype and proliferation of intestinal fibroblasts. Am J Physiol Gastrointest Liver Physiol 283:G809–G818PubMed
48.
Vallance BA, Gunawan MI, Hewlett B, et al. (2005) TGF-beta1 gene transfer to the mouse colon leads to intestinal fibrosis. Am J Physiol Gastrointest Liver Physiol 289:G116–G128PubMedCrossRef
49.
Burke JP, Ferrante M, Dejaegher K, et al. (2008) Transcriptomic analysis of intestinal fibrosis-associated gene expression in response to medical therapy in Crohn’s disease. Inflamm Bowel Dis 14:1197–1204PubMedCrossRef
50.
Berton A, Levi-Schaffer F, Emonard H, et al. (2000) Activation of fibroblasts in collagen lattices by mast cell extract: a model of fibrosis. Clin Exp Allergy 30:485–492PubMedCrossRef
51.
Xu X, Rivkind A, Pikarsky A, et al. (2004) Mast cells and eosinophils have a potential profibrogenic role in Crohn disease. Scand J Gastroenterol 39:440–447PubMedCrossRef
52.
Leeb SN, Vogl D, Grossmann J, et al. (2004) Autocrine fibronectin-induced migration of human colonic fibroblasts. Am J Gastroenterol 99:335–340PubMedCrossRef
53.
Leeb SN, Vogl D, Gunckel M, et al. (2003) Reduced migration of fibroblasts in inflammatory bowel disease: role of inflammatory mediators and focal adhesion kinase. Gastroenterology 125:1341–1354PubMedCrossRef
Metadaten
Titel
Insight into Crohn’s disease pathomorphology
verfasst von
Jonas Mudter
Markus F. Neurath
Publikationsdatum
01.12.2012
Verlag
Springer-Verlag
Erschienen in
Abdominal Radiology / Ausgabe 6/2012
Print ISSN: 2366-004X
Elektronische ISSN: 2366-0058
DOI
https://doi.org/10.1007/s00261-012-9885-3

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