Intestinal epithelial cells in inflammatory bowel diseases.
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.
Roda
Giulia
G
Department of Clinical Medicine, University of Bologna, Gastroenterology Unit, S. Orsola - Malpighi Hospital, 40138 Bologna, Italy. giuliaroda@gmail.com
Sartini
Alessandro
A
Zambon
Elisabetta
E
Calafiore
Andrea
A
Marocchi
Margherita
M
Caponi
Alessandra
A
Belluzzi
Andrea
A
Roda
Enrico
E
D000818:Animals; D001419:Bacteria / Q000472:pathogenicity; D023082:Defensins / Q000502:physiology; D006801:Humans; D007113:Immunity, Innate; D015212:Inflammatory Bowel Diseases / Q000209:etiology*; D007413:Intestinal Mucosa / Q000276:immunology / Q000502:physiology*; D008214:Lymphocytes / Q000502:physiology; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000502:physiology
D023082:Defensins; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; D051193:Toll-Like Receptors
Science. 1996 Oct 11;274(5285):262-5
8824194
Nat Rev Immunol. 2008 Jun;8(6):411-20
18469830
J Immunol. 2005 May 1;174(9):5814-22
15843585
Nat Rev Immunol. 2008 Jun;8(6):458-66
18500230
Science. 2008 Feb 8;319(5864):777-82
18218863
J Dig Dis. 2007 Nov;8(4):171-8
17970872
Int J Tissue React. 1986;8(1):79-84
3949447
Clin Exp Immunol. 2008 Jan;151(1):34-41
17991289
Ann N Y Acad Sci. 2009 May;1165:323-6
19538323
Gastroenterology. 2002 Nov;123(5):1516-26
12404227
Ann N Y Acad Sci. 2004 Dec;1029:22-35
15681740
Gastroenterology. 2008 Jan;134(1):192-203
18045591
Biochem Biophys Res Commun. 2007 Jun 22;358(1):349-55
17482139
J Histochem Cytochem. 2007 May;55(5):505-13
17242463
J Immunol. 2003 Dec 1;171(11):6164-72
14634132
Nat Rev Mol Cell Biol. 2003 Sep;4(9):721-32
14506475
Inflamm Bowel Dis. 2001 Feb;7(1):43-50
11233660
J Clin Invest. 2007 Jun;117(6):1566-74
17525800
Semin Immunol. 2001 Jun;13(3):163-76
11394959
J Cell Biol. 1995 Apr;129(2):489-506
7721948
Immunity. 2009 Sep 18;31(3):368-76
19766080
J Biol Chem. 1997 May 9;272(19):12786-92
9139738
J Biol Chem. 1999 Sep 10;274(37):26259-65
10473580
Inflamm Bowel Dis. 2009 Dec;15(12):1775-83
19637360
Gut. 2004 Nov;53(11):1658-64
15479689
Curr Opin Gastroenterol. 2007 Jul;23(4):370-8
17545771
Clin Exp Immunol. 1990 Aug;81(2):301-5
2117510
Immunol Rev. 2005 Aug;206:160-76
16048548
Immunol Rev. 2007 Feb;215:243-53
17291293
Cancer Res. 2005 Mar 15;65(6):2193-8
15781631
J Clin Invest. 2008 Feb;118(2):545-59
18188453
Immunology. 2008 Oct;125(2):145-53
18798918
Mucosal Immunol. 2008 Nov;1 Suppl 1:S5-9
19079230
Immunity. 2009 Sep 18;31(3):377-88
19766081
J Biol Chem. 2006 Jan 27;281(4):2005-11
16319062
Gastroenterology. 2009 Jul;137(1):209-20
19303021
J Gastroenterol Hepatol. 2009 Feb;24(2):202-8
19215333
World J Gastroenterol. 2008 Jan 21;14(3):401-7
18200662
Histochem Cell Biol. 2008 Jul;130(1):1-20
18365233
Inflamm Bowel Dis. 2003 Jul;9(4):215-23
12902844
Nature. 2007 Jul 26;448(7152):427-34
17653185
Mol Immunol. 2003 Nov;40(7):463-7
14568393
Am J Physiol Gastrointest Liver Physiol. 2007 Jun;292(6):G1630-40
17347451
Cell Mol Life Sci. 1997 Dec;53(11-12):888-903
9447240
J Clin Invest. 1997 Oct 15;100(8):2062-71
9329971
FASEB J. 2000 Sep;14(12):1749-53
10973924
J Allergy Clin Immunol. 2009 Jul;124(1):3-20; quiz 21-2
19560575
Pediatrics. 2003 Jun;111(6 Pt 3):1595-600
12777598
Inflamm Bowel Dis. 2009 Jan;15(1):100-13
18623167
Gastroenterology. 2005 Aug;129(2):550-64
16083712
Clin Dev Immunol. 2008;2008:639803
18350123
Lab Invest. 2004 Mar;84(3):282-91
14767487
Am J Physiol Gastrointest Liver Physiol. 2001 May;280(5):G922-9
11292601
Am J Physiol Gastrointest Liver Physiol. 2006 Mar;290(3):G496-504
16474009
Biochem Biophys Res Commun. 1996 Jul 16;224(2):397-405
8702401
Gastroenterology. 2003 Jul;125(1):47-57
12851870
Eur J Immunol. 2004 Jul;34(7):2052-9
15214053
Nat Rev Immunol. 2009 Nov;9(11):799-809
19855405
Eur J Med Res. 2004 Oct 29;9(10):456-60
15546811
Clin Immunol. 2002 Mar;102(3):267-74
11890713
Ann N Y Acad Sci. 2009 May;1165:294-300
19538319
Gastroenterology. 2006 Feb;130(2):398-411
16472595
Gastroenterology. 2004 Aug;127(2):412-21
15300573
Inflamm Bowel Dis. 2007 Aug;13(8):963-70
17455202
Biochim Biophys Acta. 2008 Mar;1778(3):660-9
17854762
Gut. 2007 Jan;56(1):61-72
16822808
Gastroenterology. 1998 Apr;114(4):697-705
9516390
J Cell Physiol. 1999 Oct;181(1):55-66
10457353
Gastroenterology. 2004 May;126(5):1347-57
15131796
J Cell Sci. 2000 Jun;113 ( Pt 11):2085-90
10806119