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PMID: 20818809 Published · ppublish English Journal Article Review

Intestinal epithelial cells in inflammatory bowel diseases.

World journal of gastroenterology ·Vol. 16 ·No. 34 ·2010-09-14 ·Pages 4264-71

Roda G, Sartini A, Zambon E, Calafiore A, Marocchi M, Caponi A, Belluzzi A, Roda E

Abstract

The pathogenesis of inflammatory bowel diseases (IBDs) seems to involve a primary defect in one or more of the elements responsible for the maintenance of intestinal homeostasis and oral tolerance. The most important element is represented by the intestinal barrier, a complex system formed mostly by intestinal epithelial cells (IECs). IECs have an active role in producing mucus and regulating its composition; they provide a physical barrier capable of controlling antigen traffic through the intestinal mucosa. At the same time, they are able to play the role of non-professional antigen presenting cells, by processing and presenting antigens directly to the cells of the intestinal immune system. On the other hand, immune cells regulate epithelial growth and differentiation, producing a continuous bi-directional cross-talk within the barrier. Several alterations of the barrier function have been identified in IBD, starting from mucus features up to its components, from epithelial junctions up to the Toll-like receptors, and altered immune responses. It remains to be understood whether these defects are primary causes of epithelial damage or secondary effects. We review the possible role of the epithelial barrier and particularly describe the role of IECs in the pathogenesis of IBD.

MeSH Terms
Animals Bacteria/pathogenicity Defensins/physiology Humans Immunity, Innate Inflammatory Bowel Diseases/etiology Intestinal Mucosa/immunology,physiology Lymphocytes/physiology Nod2 Signaling Adaptor Protein/genetics Signal Transduction Toll-Like Receptors/physiology
Chemicals
Defensins NOD2 protein, human Nod2 Signaling Adaptor Protein Toll-Like Receptors
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Roda Giulia
Department of Clinical Medicine, University of Bologna, Gastroenterology Unit, S. Orsola - Malpighi Hospital, 40138 Bologna, Italy. giuliaroda@gmail.com
Sartini Alessandro
Zambon Elisabetta
Calafiore Andrea
Marocchi Margherita
Caponi Alessandra
Belluzzi Andrea
Roda Enrico
References (70)
70 references, click to expand
  1. Impaired defense of intestinal mucosa in mice lacking intestinal trefoil factor.
    Science. 1996 Oct 11;274(5285):262-5 PMID: 8824194
  2. Epithelial-cell recognition of commensal bacteria and maintenance of immune homeostasis in the gut.
    Nat Rev Immunol. 2008 Jun;8(6):411-20 PMID: 18469830
  3. Defects in CD8+ regulatory T cells in the lamina propria of patients with inflammatory bowel disease.
    J Immunol. 2005 May 1;174(9):5814-22 PMID: 15843585
  4. The genetics and immunopathogenesis of inflammatory bowel disease.
    Nat Rev Immunol. 2008 Jun;8(6):458-66 PMID: 18500230
  5. Innate immune homeostasis by the homeobox gene caudal and commensal-gut mutualism in Drosophila.
    Science. 2008 Feb 8;319(5864):777-82 PMID: 18218863
  6. Inflammatory bowel disease: progress and current concepts of etiopathogenesis.
    J Dig Dis. 2007 Nov;8(4):171-8 PMID: 17970872
  7. Differential diagnosis of Crohn's disease of the colon from ulcerative colitis: ultrastructure study with the scanning electron microscope.
    Int J Tissue React. 1986;8(1):79-84 PMID: 3949447
  8. Increased expression of Toll-like receptor (TLR) 2 and TLR4 in the colonic mucosa of children with inflammatory bowel disease.
    Clin Exp Immunol. 2008 Jan;151(1):34-41 PMID: 17991289
  9. Lymphoepithelial interactions: a new paradigm.
    Ann N Y Acad Sci. 2009 May;1165:323-6 PMID: 19538323
  10. Expansion of CD8+ T cells with regulatory function after interaction with intestinal epithelial cells.
    Gastroenterology. 2002 Nov;123(5):1516-26 PMID: 12404227
  11. Activation of a unique population of CD8(+) T cells by intestinal epithelial cells.
    Ann N Y Acad Sci. 2004 Dec;1029:22-35 PMID: 15681740
  12. Epithelial: lamina propria lymphocyte interactions promote epithelial cell differentiation.
    Gastroenterology. 2008 Jan;134(1):192-203 PMID: 18045591
  13. Denatured human alpha-defensin attenuates the bactericidal activity and the stability against enzymatic digestion.
    Biochem Biophys Res Commun. 2007 Jun 22;358(1):349-55 PMID: 17482139
  14. Tissue localization of human trefoil factors 1, 2, and 3.
    J Histochem Cytochem. 2007 May;55(5):505-13 PMID: 17242463
  15. Proinflammatory cytokines disrupt epithelial barrier function by apoptosis-independent mechanisms.
    J Immunol. 2003 Dec 1;171(11):6164-72 PMID: 14634132
  16. Trefoil factors: initiators of mucosal healing.
    Nat Rev Mol Cell Biol. 2003 Sep;4(9):721-32 PMID: 14506475
  17. Paneth cell defensins and innate immunity of the small bowel.
    Inflamm Bowel Dis. 2001 Feb;7(1):43-50 PMID: 11233660
  18. CEACAM6 acts as a receptor for adherent-invasive E. coli, supporting ileal mucosa colonization in Crohn disease.
    J Clin Invest. 2007 Jun;117(6):1566-74 PMID: 17525800
  19. The role of epithelial cells in immune regulation in the gut.
    Semin Immunol. 2001 Jun;13(3):163-76 PMID: 11394959
  20. In vivo analysis of cadherin function in the mouse intestinal epithelium: essential roles in adhesion, maintenance of differentiation, and regulation of programmed cell death.
    J Cell Biol. 1995 Apr;129(2):489-506 PMID: 7721948
  21. Immune responses to the microbiota at the intestinal mucosal surface.
    Immunity. 2009 Sep 18;31(3):368-76 PMID: 19766080
  22. Characterization of a 180-kDa intestinal epithelial cell membrane glycoprotein, gp180. A candidate molecule mediating t cell-epithelial cell interactions.
    J Biol Chem. 1997 May 9;272(19):12786-92 PMID: 9139738
  23. The nonclassical class I molecule CD1d associates with the novel CD8 ligand gp180 on intestinal epithelial cells.
    J Biol Chem. 1999 Sep 10;274(37):26259-65 PMID: 10473580
  24. Defect in CEACAM family member expression in Crohn's disease IECs is regulated by the transcription factor SOX9.
    Inflamm Bowel Dis. 2009 Dec;15(12):1775-83 PMID: 19637360
  25. NOD2 (CARD15) mutations in Crohn's disease are associated with diminished mucosal alpha-defensin expression.
    Gut. 2004 Nov;53(11):1658-64 PMID: 15479689
  26. Defensins and other antimicrobial peptides in inflammatory bowel disease.
    Curr Opin Gastroenterol. 2007 Jul;23(4):370-8 PMID: 17545771
  27. Tumour necrosis factor-alpha and interferon-gamma production measured at the single cell level in normal and inflamed human intestine.
    Clin Exp Immunol. 1990 Aug;81(2):301-5 PMID: 2117510
  28. Non-classical MHC class I molecules on intestinal epithelial cells: mediators of mucosal crosstalk.
    Immunol Rev. 2005 Aug;206:160-76 PMID: 16048548
  29. Epithelia: lymphocyte interactions in the gut.
    Immunol Rev. 2007 Feb;215:243-53 PMID: 17291293
  30. Expression of the carcinoembryonic antigen gene is inhibited by SOX9 in human colon carcinoma cells.
    Cancer Res. 2005 Mar 15;65(6):2193-8 PMID: 15781631
  31. Muramyl dipeptide activation of nucleotide-binding oligomerization domain 2 protects mice from experimental colitis.
    J Clin Invest. 2008 Feb;118(2):545-59 PMID: 18188453
  32. The role of T-regulatory cells and Toll-like receptors in the pathogenesis of human inflammatory bowel disease.
    Immunology. 2008 Oct;125(2):145-53 PMID: 18798918
  33. The molecular basis of NOD2 susceptibility mutations in Crohn's disease.
    Mucosal Immunol. 2008 Nov;1 Suppl 1:S5-9 PMID: 19079230
  34. The multifaceted influence of the mucosal microflora on mucosal dendritic cell responses.
    Immunity. 2009 Sep 18;31(3):377-88 PMID: 19766081
  35. NOD2/CARD15 mediates induction of the antimicrobial peptide human beta-defensin-2.
    J Biol Chem. 2006 Jan 27;281(4):2005-11 PMID: 16319062
  36. Colitis-associated variant of TLR2 causes impaired mucosal repair because of TFF3 deficiency.
    Gastroenterology. 2009 Jul;137(1):209-20 PMID: 19303021
  37. Defensins and inflammation: the role of defensins in inflammatory bowel disease.
    J Gastroenterol Hepatol. 2009 Feb;24(2):202-8 PMID: 19215333
  38. Role of the intestinal barrier in inflammatory bowel disease.
    World J Gastroenterol. 2008 Jan 21;14(3):401-7 PMID: 18200662
  39. Organization of multiprotein complexes at cell-cell junctions.
    Histochem Cell Biol. 2008 Jul;130(1):1-20 PMID: 18365233
  40. Inducible and constitutive beta-defensins are differentially expressed in Crohn's disease and ulcerative colitis.
    Inflamm Bowel Dis. 2003 Jul;9(4):215-23 PMID: 12902844
  41. Unravelling the pathogenesis of inflammatory bowel disease.
    Nature. 2007 Jul 26;448(7152):427-34 PMID: 17653185
  42. Alpha-defensins in the gastrointestinal tract.
    Mol Immunol. 2003 Nov;40(7):463-7 PMID: 14568393
  43. Intestinal epithelial cells from inflammatory bowel disease patients preferentially stimulate CD4+ T cells to proliferate and secrete interferon-gamma.
    Am J Physiol Gastrointest Liver Physiol. 2007 Jun;292(6):G1630-40 PMID: 17347451
  44. Trefoil peptides: from structure to function.
    Cell Mol Life Sci. 1997 Dec;53(11-12):888-903 PMID: 9447240
  45. Defective expression of gp180, a novel CD8 ligand on intestinal epithelial cells, in inflammatory bowel disease.
    J Clin Invest. 1997 Oct 15;100(8):2062-71 PMID: 9329971
  46. Leaks in the epithelial barrier caused by spontaneous and TNF-alpha-induced single-cell apoptosis.
    FASEB J. 2000 Sep;14(12):1749-53 PMID: 10973924
  47. Intestinal barrier function: molecular regulation and disease pathogenesis.
    J Allergy Clin Immunol. 2009 Jul;124(1):3-20; quiz 21-2 PMID: 19560575
  48. Mucosal immunity.
    Pediatrics. 2003 Jun;111(6 Pt 3):1595-600 PMID: 12777598
  49. Intestinal barrier dysfunction in inflammatory bowel diseases.
    Inflamm Bowel Dis. 2009 Jan;15(1):100-13 PMID: 18623167
  50. Interleukin-13 is the key effector Th2 cytokine in ulcerative colitis that affects epithelial tight junctions, apoptosis, and cell restitution.
    Gastroenterology. 2005 Aug;129(2):550-64 PMID: 16083712
  51. Feeding our immune system: impact on metabolism.
    Clin Dev Immunol. 2008;2008:639803 PMID: 18350123
  52. A porous defense: the leaky epithelial barrier in intestinal disease.
    Lab Invest. 2004 Mar;84(3):282-91 PMID: 14767487
  53. The adherent gastrointestinal mucus gel layer: thickness and physical state in vivo.
    Am J Physiol Gastrointest Liver Physiol. 2001 May;280(5):G922-9 PMID: 11292601
  54. Molecular mechanism of tumor necrosis factor-alpha modulation of intestinal epithelial tight junction barrier.
    Am J Physiol Gastrointest Liver Physiol. 2006 Mar;290(3):G496-504 PMID: 16474009
  55. Quantitative analysis of MUC2 synthesis in ulcerative colitis.
    Biochem Biophys Res Commun. 1996 Jul 16;224(2):397-405 PMID: 8702401
  56. Crohn's disease and the NOD2 gene: a role for paneth cells.
    Gastroenterology. 2003 Jul;125(1):47-57 PMID: 12851870
  57. NOD2 mediates anti-inflammatory signals induced by TLR2 ligands: implications for Crohn's disease.
    Eur J Immunol. 2004 Jul;34(7):2052-9 PMID: 15214053
  58. Intestinal mucosal barrier function in health and disease.
    Nat Rev Immunol. 2009 Nov;9(11):799-809 PMID: 19855405
  59. Increased intestinal permeability in patients with inflammatory bowel disease.
    Eur J Med Res. 2004 Oct 29;9(10):456-60 PMID: 15546811
  60. A non-class I MHC intestinal epithelial surface glycoprotein, gp180, binds to CD8.
    Clin Immunol. 2002 Mar;102(3):267-74 PMID: 11890713
  61. Epithelial tight junctions in intestinal inflammation.
    Ann N Y Acad Sci. 2009 May;1165:294-300 PMID: 19538319
  62. Chitinase 3-like-1 exacerbates intestinal inflammation by enhancing bacterial adhesion and invasion in colonic epithelial cells.
    Gastroenterology. 2006 Feb;130(2):398-411 PMID: 16472595
  63. High prevalence of adherent-invasive Escherichia coli associated with ileal mucosa in Crohn's disease.
    Gastroenterology. 2004 Aug;127(2):412-21 PMID: 15300573
  64. Viscosity gradient within the mucus layer determines the mucosal barrier function and the spatial organization of the intestinal microbiota.
    Inflamm Bowel Dis. 2007 Aug;13(8):963-70 PMID: 17455202
  65. Adherens and tight junctions: structure, function and connections to the actin cytoskeleton.
    Biochim Biophys Acta. 2008 Mar;1778(3):660-9 PMID: 17854762
  66. Changes in expression and distribution of claudin 2, 5 and 8 lead to discontinuous tight junctions and barrier dysfunction in active Crohn's disease.
    Gut. 2007 Jan;56(1):61-72 PMID: 16822808
  67. Rapid mitogen-activated protein kinase activation by transforming growth factor alpha in wounded rat intestinal epithelial cells.
    Gastroenterology. 1998 Apr;114(4):697-705 PMID: 9516390
  68. Transforming growth factor-beta1 preserves epithelial barrier function: identification of receptors, biochemical intermediates, and cytokine antagonists.
    J Cell Physiol. 1999 Oct;181(1):55-66 PMID: 10457353
  69. The expression and function of costimulatory molecules B7H and B7-H1 on colonic epithelial cells.
    Gastroenterology. 2004 May;126(5):1347-57 PMID: 15131796
  70. Expression from the human occludin promoter is affected by tumor necrosis factor alpha and interferon gamma.
    J Cell Sci. 2000 Jun;113 ( Pt 11):2085-90 PMID: 10806119
Article Info
Journal
World journal of gastroenterology
Abbr.
World J Gastroenterol
ISSN
2219-2840
Published
2010-09-14
Pages
4264-71
Language
English
Region
United States
NLM ID
100883448
PMCID
PMC2937106
Subset
IM
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