Año 2015 / Volumen 107 / Número 11
Revisión
Función barrera intestinal y su implicación en enfermedades digestivas

686-696

DOI: 10.17235/reed.2015.3846/2015

Eloísa Salvo Romero, Carmen Alonso Cotoner, Cristina Pardo Camacho, Maite Casado Bedmar, María Vicario,

Resumen
La superficie de la mucosa del tracto gastrointestinal está revestida de células epiteliales que establecen una barrera efectiva, mediante uniones intercelulares, entre el medio interno y el medio externo, impidiendo el paso de sustancias potencialmente nocivas. Sin embargo las células epiteliales también son responsables de la absorción de nutrientes y electrolitos, por lo que se requiere una barrera semipermeable que permita el paso selectivo a ciertas sustancias, mientras que evite el acceso a otras. Para ello, el intestino ha desarrollado la “función barrera intestinal”, un sistema defensivo compuesto por diferentes elementos, tanto extracelulares como celulares, que actúan de forma coordinada para impedir el paso de antígenos, toxinas y productos microbianos y, a la vez, mantiene el correcto desarrollo de la barrera epitelial, el sistema inmunitario y la adquisición de tolerancia hacia los antígenos de la dieta y la microbiota intestinal. La alteración de los mecanismos que componen la función barrera favorece el desarrollo de respuestas inmunitarias exageradas, y, aunque se desconoce su implicación exacta, la alteración de la función barrera intestinal se ha asociado al desarrollo de enfermedades inflamatorias en el tracto digestivo. En esta revisión se detallan los diferentes elementos que componen la función barrera intestinal y las alteraciones moleculares y celulares más características descritas en enfermedades digestivas asociadas a la disfunción de este mecanismo de defensa.
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Bibliografía
1. Artis D. Epithelial-cell recognition of commensal bacteria and maintenance of immune homeostasis in the gut. Nat Rev Immunol 2008; 8: 411-20.
2. Turner J. Intestinal mucosal barrier function in health and disease. Nat Rev Immunol 2009; 9: 799-809.
3. Caricilli A, Castoldi A, Cámara N. Intestinal barrier: A gentlemen's agreement between microbiota and immunity. World J Gastrointest Pathophysiol 2014; 5: p. 18-32.
4. Rescigno M. The intestinal epithelial barrier in the control of homeostasis and immunity. Trends Immunol 2011; 32: 256-64.
5. Pascual S, Martínez J, Pérez-Mateo M. The intestinal barrier: functional disorders in digestive and non-digestive diseases. Gastroenterol Hepatol 2001; 24: 256-67.
6. Shen L, Turner J. Role of epithelial cells in initiation and propagation of intestinal inflammation. Eliminating the static: tight junction dynamics exposed. Am J Physiol Gastrointest Liver Physiol 2006; 290: G577-82.
7. Sarker S, Gyr K. Non-immunological defence mechanisms of the gut. Gut. 1992; 33(7): p. 987-93.
8. Qin X, Caputo F, Xu D, et al. Hydrophobicity of mucosal surface and its relationship to gut barrier function. Shock 2008; 29: 372-6.
9. Bevins C, Salzman N. Paneth cells, antimicrobial peptides and maintenance of intestinal homeostasis. Nat Rev Microbiol 2011; 9: 356-68.
10. Antoni L, Nuding S, Weller D, et al. Human colonic mucus is a reservoir for antimicrobial peptides. J Crohns Colitis 2013; 7: 652-64.
11. Brandtzaeg P. Molecular and cellular aspects of the secretory immunoglobulin system. APMIS 1995; 103: 1-19.
12. Elphick D, Mahida Y. Paneth cells: their role in innate immunity and inflammatory disease. Gut 2005; 54: 1802-9.
13. Lence WI, Cheung G, Strohmeier G, et al. Induction of epithelial chloride secretion by channel-forming cryptdins 2 and 3. Proc Natl Acad Sci U S A 1997; 94: 8585-9.
14. Salzman N, Hung K, Haribhai D, et al. Enteric defensins are essential regulators of intestinal microbial ecology. Nat Immunol 2010; 11(1): p. 76-83.
15. Ugolev A, De Laey P. Membrane digestion. A concept of enzyme hydrolysis on cell membranes. Biochim Biophys Acta 1973; 300: 105-28.
16. Shan M, Gentile M, Yeiser J, et al. Mucus enhances gut homeostasis and oral tolerance by delivering immunoregulatory signals. Science 2013; 342: 447-53.
17. Chang E, Rao M. Intestinal water and electrolyte transport: mechanisms of physiological and adaptive responses. In Johnson LR,ADH. Physiology of the Gastrointestinal Tract (3rd ed.). 3rd ed. New York: Raven,: Lippincott Williams & Wilkins; 1994. p. 2027–2081.
18. Neish A. Microbes in gastrointestinal health and disease. Gastroenterology 2009; 136: 65-80.
19. Palmer C, Bik E, DiGiulio D, et al. Development of the human infant intestinal microbiota. PLoS Biol 2007; 5: e177.
20. Tappenden K, Deutsch A. The physiological relevance of the intestinal microbiota-contributions to human health. J Am Coll Nutr 2007; 26: 679S-83S.
21. Booth C, Potten C. Gut instincts: thoughts on intestinal epithelial stem cells. J Clin Invest 2000; 105: 1493-9.
22. Van Der Flier L, Clevers H. Stem cells, self-renewal, and differentiation in the intestinal epithelium. Annu Rev Physiol 2009; 71: 241–60.
23. Pott J, Hornef M. Innate immune signalling at the intestinal epithelium in homeostasis and disease. EMBO Rep 2012; 13: 684-98.
24. Zeuthen L, Fink L, Frokiaer H. Epithelial cells prime the immune response to an array of gut-derived commensals towards a tolerogenic phenotype through distinct actions of thymic stromal lymphopoietin and transforming growth factor-beta. Immunology 2008; 123: 197-208.
25. Zaph C, Du Y, Saenz S, et al. Commensal-dependent expression of IL-25 regulates the IL-23-IL-17 axis in the intestine. J Exp Med. 2008; 205: 2191-8.
26. He B, Xu W, Santini P, et al. Intestinal bacteria trigger T cell-independent immunoglobulin A(2) class switching by inducing epithelial-cell secretion of the cytokine APRIL. Immunity 2007; 26: 812-26.
27. Xu W, He B, Chiu A, et al. Epithelial cells trigger frontline immunoglobulin class switching through a pathway regulated by the inhibitor SLPI. Nat Immunol 2007; 8: 294-303.
28. Cerutti A, Rescigno M. The biology of intestinal immunoglobulin A responses. Immunity 2008; 28: 740-50.
29. Corr S, Gahan C, Hill C. M-cells: origin, morphology and role in mucosal immunity and microbial pathogenesis. FEMS Immunol Med Microbiol 2008; 52: 2-12.
30. Miller H, Zhang J, Kuolee R, et al. Intestinal M cells: the fallible sentinels? World J Gastroenterol 2007; 13: 1477-86.
31. Gill N, Wlodarska M, Finlay B. Roadblocks in the gut: barriers to enteric infection. Cell Microbiol 2011; 13: 660-9.
32. Göke M, Kanai M, Podolsky D. Intestinal fibroblasts regulate intestinal epithelial cell proliferation via hepatocyte growth factor. Am J Physiol 1998; 274: G809-18.
33. Furness J. Types of neurons in the enteric nervous system. J Auton Nerv Syst 2000; 81: 87-96.
34. Rühl A. Glial cells in the gut. Neurogastroenterol Motil 2005; 17: 777-90.
35. Flemström G, Sjöblom M. Epithelial cells and their neighbors. INew perspectives on efferent signaling between brain, neuroendocrine cells, and gut epithelial cells. Am J Physiol Gastrointest Liver Physiol 2005; 289: G377-80.
36. Balda M, Matter K. Tight junctions at a glance. J Cell Sci 2008; 121: 3677-82.
37. Schulzke J, Fromm M. Tight junctions: molecular structure meets function. Ann N Y Acad Sci 2009; 1165: 1-6.
38. Bauer H, Stelzhammer W, Fuchs R, et al. Astrocytes and neurons express the tight junction-specific protein occludin in vitro. Exp Cell Res 1999; 250: 434-8.
39. Blank F, Wehrli M, Lehmann A, et al. Macrophages and dendritic cells express tight junction proteins and exchange particles in an in vitro model of the human airway wall. Immunobiology 2011; 216: 86-95.
40. Rao R. Occludin phosphorylation in regulation of epithelial tight junctions. Ann N Y Acad Sci 2009; 1165: 62-8.
41. Dörfel M, Huber O. Modulation of tight junction structure and function by kinases and phosphatases targeting occludin. J Biomed Biotechnol 2012; 2012: 807356.
42. Hartsock A, Nelson W. Adherens and tight junctions: structure, function and connections to the actin cytoskeleton. Biochim Biophys Acta 2008; 1778: 660-9.
43. Escaffit F, Boudreau F, Beaulieu J. Differential expression of claudin-2 along the human intestine: Implication of GATA-4 in the maintenance of claudin-2 in differentiating cells. J Cell Physiol 2005; 203: 15-26.
44. Liu Y, Nusrat A, Schnell F, et al. Human junction adhesion molecule regulates tight junction resealing in epithelia. J Cell Sci 2000; 113: 2363-74.
45. Laukoetter M, Nava P, Lee W, et al. JAM-A regulates permeability and inflammation in the intestine in vivo. J Exp Med 2007; 204: 3067-76.
46. Ikenouchi J, Furuse M, Furuse K, et al. Tricellulin constitutes a novel barrier at tricellular contacts of epithelial cells. J Cell Biol 2005; 171: 939-45.
47. Mariano C, Sasaki H, Brites D, et al. A look at tricellulin and its role in tight junction formation and maintenance. Eur J Cell Biol 2011; 90: 787-96.
48. Umeda K, Ikenouchi J, Katahira-Tayama S, et al. ZO-1 and ZO-2 independently determine where claudins are polymerized in tight-junction strand formation. Cell 2006; 126: 741-54.
49. Niessen C, Gottardi C. Molecular components of the adherens junction. Biochim Biophys Acta. 2008; 1778: 562-71.
50. Garrod D, Chidgey M. Desmosome structure, composition and function. Biochim Biophys Acta 2008; 1778: 572-87.
51. Kojima T, Murata M, Go M, et al. Connexins induce and maintain tight junctions in epithelial cells. J Membr Biol 2007; 217: 13-9.
52. Macdonald T, Monteleone G. Immunity, inflammation, and allergy in the gut. Science 2005; 307: 1920-5.
53. Rhee S, Im E, Riegler M, et al. Pathophysiological role of Toll-like receptor 5 engagement by bacterial flagellin in colonic inflammation. Proc Natl Acad Sci U S A 2005; 102: 13610-5.
54. Lee J, Mo J, Katakura K, et al. Maintenance of colonic homeostasis by distinctive apical TLR9 signalling in intestinal epithelial cells. Nat Cell Biol 2006; 8: 1327-36.
55. Yan F, Polk D. Disruption of NF-kappaB signalling by ancient microbial molecules: novel therapies of the future? Gut 2010; 59: 421-6.
56. Sansonetti P. War and peace at mucosal surfaces. Nat Rev Immunol 2004; 4: 953-64.
57. Bernardo D. Human intestinal dendritic cells as controllers of mucosal immunity. Rev Esp Enferm Dig 2013; 105: 279-90.
58. Blander J, Sander L. Beyond pattern recognition: five immune checkpoints for scaling the microbial threat. Nat Rev Immunol 2012; 12: 215-25.
59. Sansonetti P. To be or not to be a pathogen: that is the mucosally relevant question. Mucosal Immunol 2011; 4: 8-14.
60. Montalvillo E, Garrote J, Bernardo D, et al. Innate lymphoid cells and natural killer T cells in the gastrointestinal tract immune system. Rev Esp Enferm Dig 2014; 106: 334-45.
61. Kato L, Kawamoto S, Maruya M, et al. The role of the adaptive immune system in regulation of gut microbiota. Immunol Rev 2014; 260: 67-75.
62. Maynard C, Weaver C. Intestinal effector T cells in health and disease. Immunity. 2009; 31: 389-400.
63. Khor B, Gardet A, Xavier R. Genetics and pathogenesis of inflammatory bowel disease. Nature 2011; 474: 307-17.
64. Turner J. Intestinal mucosal barrier function in health and disease. Nat Rev Immunol 2009; 9: 799-809.
65. Keita A, Söderholm J. The intestinal barrier and its regulation by neuroimmune factors. Neurogastroenterol Motil 2010; 22: 718-33.
66. Conner S, Schmid S. Regulated portals of entry into the cell. Nature 2003; 422: 37-44.
67. Utech M, Mennigen R, Bruewer M. Endocytosis and recycling of tight junction proteins in inflammation. J Biomed Biotechnol 2010; 2010:484987.
68. Prasad S, Mingrino R, Kaukinen K, et al. Inflammatory processes have differential effects on claudins 2, 3 and 4 in colonic epithelial cells. Lab Invest 2005; 85: 1139-62.
69. Schulzke J, Bojarski C, Zeissig S, et al. Disrupted barrier function through epithelial cell apoptosis. Ann N Y Acad Sci 2006; 1072: 288-99.
70. Wells J, Rossi O, Meijerink M, et al. Epithelial crosstalk at the microbiota-mucosal interface. Proc Natl Acad Sci U S A. 2011; 1: 4607-14.
71. Wang F, Graham W, Wang Y, et al. Interferon-gamma and tumor necrosis factor-alpha synergize to induce intestinal epithelial barrier dysfunction by up-regulating myosin light chain kinase expression. Am J Pathol 2005; 166: 409-19.
72. Al-Sadi R, Ye D, Dokladny K, et al. Mechanism of IL-1beta-induced increase in intestinal epithelial tight junction permeability. J Immunol 2008; 180: 5653-61.
73. Al-Sadi R, Boivin M, Ma T. Mechanism of cytokine modulation of epithelial tight junction barrier. Front Biosci 2009; 14: 2765-78.
74. Neunlist M, Toumi F, Oreschkova T, et al. Human ENS regulates the intestinal epithelial barrier permeability and a tight junction-associated protein ZO-1 via VIPergic pathways. Am J Physiol Gastrointest Liver Physiol 2003; 285: G1028-36.
75. Savidge T, Newman P, Pothoulakis C, et al. Enteric glia regulate intestinal barrier function and inflammation via release of S-nitrosoglutathione. Gastroenterology 2007; 132: 1344-58.
76. Zeissig S, Bürgel N, Günzel D, et al. 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; 56: 61-72.
77. Blair S, Kane S, Clayburgh D, et al. Epithelial myosin light chain kinase expression and activity are upregulated in inflammatory bowel disease. Lab Invest 2006; 86: 191-201.
78. MacDonald T, Hutchings P, Choy M, et al. Tumour necrosis factor-alpha and interferon-gamma production measured at the single cell level in normal and inflamed human intestine. Clin Exp Immunol 1990; 81: 301-5.
79. Madara J, Stafford J. Interferon-gamma directly affects barrier function of cultured intestinal epithelial monolayers. J Clin Invest 1989; 83: 724-7.
80. Kaser A, Lee A, Franke A, et al. XBP1 links ER stress to intestinal inflammation and confers genetic risk for human inflammatory bowel disease. Cell 2008; 134: 743-56.
81. Fisher S, Tremelling M, Anderson C, et al. Genetic determinants of ulcerative colitis include the ECM1 locus and five loci implicated in Crohn's disease. Nat Genet 2008; 40: 710-2.
82. Watanabe T, Asano N, Murray P, et al. Muramyl dipeptide activation of nucleotide-binding oligomerization domain 2 protects mice from experimental colitis. J Clin Invest 2008; 118: 545-59.
83. Comino I, Suligoj T, Al-Hassi H, et al. Constitutive gut-homing capacity on circulating myeloid dendritic cells in coeliac disease.. Rev Esp Enferm Dig 2014; 106: 64-5.
84. Pizzuti D, Bortolami M, Mazzon E, et al. Transcriptional downregulation of tight junction protein ZO-1 in active coeliac disease is reversed after a gluten-free diet. Dig Liver Dis 2004; 36: 337-41.
85. Sander G, Cummins A, Henshall T, et al. Rapid disruption of intestinal barrier function by gliadin involves altered expression of apical junctional proteins. FEBS Lett 2005; 579:4851-5.
86. Fasano A, Not T, Wang W, et al. Zonulin, a newly discovered modulator of intestinal permeability, and its expression in coeliac disease. Lancet 2000; 355: 1518-9.
87. Drago S, El Asmar R, Di Pierro M, et al. Gliadin, zonulin and gut permeability: Effects on celiac and non-celiac intestinal mucosa and intestinal cell lines. Scand J Gastroenterol 2006; 41: 408-19.
88. Ventura M, Polimeno L, Amoruso A, et al. Intestinal permeability in patients with adverse reactions to food. Dig Liver Dis 2006; 38: 732-6.
89. Heyman M. Gut barrier dysfunction in food allergy. Eur J Gastroenterol Hepatol 2005; 17: 1279-85.
90. Camilleri M, Lasch K, Zhou W. Irritable bowel syndrome: methods, mechanisms, and pathophysiology. The confluence of increased permeability, inflammation, and pain in irritable bowel syndrome. Am J Physiol Gastrointest Liver Physiol 2012; 303: G775-85.
91. Martínez C, González-Castro A, Vicario M, et al. Cellular and molecular basis of intestinal barrier dysfunction in the irritable bowel syndrome. Gut Liver 2012; 6: 305-15.
92. Martínez C, Lobo B, Pigrau M, et al. Diarrhoea-predominant irritable bowel syndrome: an organic disorder with structural abnormalities in the jejunal epithelial barrier. Gut 2013; 62: 1160-8.
93. Bertiaux-Vandaële N, Youmba S, Belmonte L, et al. The expression and the cellular distribution of the tight junction proteins are altered in irritable bowel syndrome patients with differences according to the disease subtype. Am J Gastroenterol. 2011; 106: 2165-73.
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Salvo Romero E, Alonso Cotoner C, Pardo Camacho C, Casado Bedmar M, Vicario M. Función barrera intestinal y su implicación en enfermedades digestivas. 3846/2015


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Recibido: 14/05/2015

Aceptado: 25/05/2015

Prepublicado: 15/09/2015

Publicado: 30/10/2015

Tiempo de revisión del artículo: 7 días

Tiempo de prepublicación: 124 días

Tiempo de edición del artículo: 169 días


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