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Unravelling the pathogenesis of inflammatory bowel disease

Nature volume 448, pages 427–434 (2007)Cite this article

Abstract

Recently, substantial advances in the understanding of the molecular pathogenesis of inflammatory bowel disease (IBD) have been made owing to three related lines of investigation. First, IBD has been found to be the most tractable of complex disorders for discovering susceptibility genes, and these have shown the importance of epithelial barrier function, and innate and adaptive immunity in disease pathogenesis. Second, efforts directed towards the identification of environmental factors implicate commensal bacteria (or their products), rather than conventional pathogens, as drivers of dysregulated immunity and IBD. Third, murine models, which exhibit many of the features of ulcerative colitis and seem to be bacteria-driven, have helped unravel the pathogenesis/mucosal immunopathology of IBD.

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Figure 1: Histologic hallmarks of IBD: clues to immunopathogenesis.
Figure 2: Patterns of IBD etiopathogenesis.
Figure 3: Several IBD susceptibility gene products modulate host-cell functional response to microbial flora.
Figure 4: Mucosal immune responses to luminal flora are multi-dimensional.

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References

  1. Podolsky, D. K. Inflammatory bowel disease. N. Engl. J. Med. 347, 417–429 (2002)

    CAS  PubMed  Google Scholar 

  2. Orholm, M. et al. Familial occurrence of inflammatory bowel disease. N. Engl. J. Med. 324, 84–88 (1991)

    CAS  PubMed  Google Scholar 

  3. Tysk, C., Lindberg, E., Jarnerot, G. & Floderus-Myrhed, B. Ulcerative colitis and Crohn's disease in an unselected population of monozygotic and dizygotic twins. A study of heritability and the influence of smoking. Gut 29, 990–996 (1988)

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Hugot, J. P. et al. Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease. Nature 411, 599–603 (2001)

    ADS  CAS  PubMed  Google Scholar 

  5. Ogura, Y. et al. A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease. Nature 411, 603–606 (2001)

    ADS  CAS  PubMed  Google Scholar 

  6. Duerr, R. H. et al. A genome-wide association study identifies IL23R as an inflammatory bowel disease gene. Science 314, 1461–1463 (2006)

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  7. Goyette, P., Labbe, C., Trinh, T. T., Xavier, R. J. & Rioux, J. D. Molecular pathogenesis of inflammatory bowel disease: genotypes, phenotypes and personalized medicine. Ann. Med. 39, 177–199 (2007)

    CAS  PubMed  Google Scholar 

  8. Hampe, J. et al. A genome-wide association scan of nonsynonymous SNPs identifies a susceptibility variant for Crohn disease in ATG16L1. Nature Genet. 39, 207–211 (2007)

    CAS  PubMed  Google Scholar 

  9. Libioulle, C. et al. Novel crohn disease locus identified by genome-wide association maps to a gene desert on 5p13.1 and modulates expression of PTGER4. PLoS Genet. 3, e58 (2007)

    PubMed  PubMed Central  Google Scholar 

  10. Peltekova, V. D. et al. Functional variants of OCTN cation transporter genes are associated with Crohn disease. Nature Genet. 36, 471–475 (2004)

    CAS  PubMed  Google Scholar 

  11. Rioux, J. D. et al. Genetic variation in the 5q31 cytokine gene cluster confers susceptibility to Crohn disease. Nature Genet. 29, 223–228 (2001)

    MathSciNet  CAS  PubMed  Google Scholar 

  12. Rioux, J. D. et al. Genome-wide association study identifies new susceptibility loci for Crohn disease and implicates autophagy in disease pathogenesis. Nature Genet. 39, 596–604 (2007)

    CAS  PubMed  Google Scholar 

  13. Silverberg, M. S. et al. Refined genomic localization and ethnic differences observed for the IBD5 association with Crohn's disease. Eur. J. Hum. Genet. 15, 328–335 (2007)

    CAS  PubMed  Google Scholar 

  14. Yamazaki, K. et al. Single nucleotide polymorphisms in TNFSF15 confer susceptibility to Crohn's disease. Hum. Mol. Genet. 14, 3499–3506 (2005)

    CAS  PubMed  Google Scholar 

  15. Gionchetti, P. et al. Prophylaxis of pouchitis onset with probiotic therapy: a double-blind, placebo-controlled trial. Gastroenterology 124, 1202–1209 (2003)

    PubMed  Google Scholar 

  16. Sutherland, L. et al. Double blind, placebo controlled trial of metronidazole in Crohn's disease. Gut 32, 1071–1075 (1991)

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Barnich, N. et al. CEACAM6 acts as a receptor for adherent-invasive E. coli, supporting ileal mucosa colonization in Crohn disease. J. Clin. Invest. 117, 1566–1574 (2007)

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Darfeuille-Michaud, A. et al. Presence of adherent Escherichia coli strains in ileal mucosa of patients with Crohn's disease. Gastroenterology 115, 1405–1413 (1998)

    CAS  PubMed  Google Scholar 

  19. Elson, C. O. et al. Experimental models of inflammatory bowel disease reveal innate, adaptive, and regulatory mechanisms of host dialogue with the microbiota. Immunol. Rev. 206, 260–276 (2005)

    PubMed  Google Scholar 

  20. Onderdonk, A. B., Hermos, J. A. & Bartlett, J. G. The role of the intestinal microflora in experimental colitis. Am. J. Clin. Nutr. 30, 1819–1825 (1977)

    CAS  PubMed  Google Scholar 

  21. Sellon, R. K. et al. Resident enteric bacteria are necessary for development of spontaneous colitis and immune system activation in interleukin-10-deficient mice. Infect. Immun. 66, 5224–5231 (1998)

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Gill, S. R. et al. Metagenomic analysis of the human distal gut microbiome. Science 312, 1355–1359 (2006)

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  23. Buhner, S. et al. Genetic basis for increased intestinal permeability in families with Crohn's disease: role of CARD15 3020insC mutation? Gut 55, 342–347 (2006)

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Irvine, E. J. & Marshall, J. K. Increased intestinal permeability precedes the onset of Crohn's disease in a subject with familial risk. Gastroenterology 119, 1740–1744 (2000)

    CAS  PubMed  Google Scholar 

  25. May, G. R., Sutherland, L. R. & Meddings, J. B. Is small intestinal permeability really increased in relatives of patients with Crohn's disease? Gastroenterology 104, 1627–1632 (1993)

    CAS  PubMed  Google Scholar 

  26. Soderholm, J. D. et al. Augmented increase in tight junction permeability by luminal stimuli in the non-inflamed ileum of Crohn's disease. Gut 50, 307–313 (2002)

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Gassler, N. et al. Inflammatory bowel disease is associated with changes of enterocytic junctions. Am. J. Physiol. Gastrointest. Liver Physiol. 281, G216–G228 (2001)

    CAS  PubMed  Google Scholar 

  28. Kabashima, K. et al. The prostaglandin receptor EP4 suppresses colitis, mucosal damage and CD4 cell activation in the gut. J. Clin. Invest. 109, 883–893 (2002)

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Cario, E. et al. Lipopolysaccharide activates distinct signaling pathways in intestinal epithelial cell lines expressing Toll-like receptors. J. Immunol. 164, 966–972 (2000)

    CAS  PubMed  Google Scholar 

  30. Hisamatsu, T. et al. CARD15/NOD2 functions as an antibacterial factor in human intestinal epithelial cells. Gastroenterology 124, 993–1000 (2003)

    CAS  PubMed  Google Scholar 

  31. Yoshida, M. et al. Neonatal Fc receptor for IgG regulates mucosal immune responses to luminal bacteria. J. Clin. Invest. 116, 2142–2151 (2006)

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Neish, A. S. et al. Prokaryotic regulation of epithelial responses by inhibition of IκB-α ubiquitination. Science 289, 1560–1563 (2000)

    ADS  CAS  PubMed  Google Scholar 

  33. Kelly, D. et al. Commensal anaerobic gut bacteria attenuate inflammation by regulating nuclear–cytoplasmic shuttling of PPAR-γ and RelA. Nature Immunol. 5, 104–112 (2004)

    CAS  Google Scholar 

  34. Nenci, A. et al. Epithelial NEMO links innate immunity to chronic intestinal inflammation. Nature 446, 557–561 (2007)

    ADS  CAS  PubMed  Google Scholar 

  35. Zaph, C. et al. Epithelial cell-intrinsic IKK-β expression regulates intestinal immune homeostasis. Nature 446, 552–556 (2007)

    ADS  CAS  PubMed  Google Scholar 

  36. Wehkamp, J. et al. NOD2 (CARD15) mutations in Crohn's disease are associated with diminished mucosal alpha-defensin expression. Gut 53, 1658–1664 (2004)

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Wehkamp, J. et al. Reduced Paneth cell α-defensins in ileal Crohn's disease. Proc. Natl Acad. Sci. USA 102, 18129–18134 (2005)

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  38. Mashimo, H., Wu, D. C., Podolsky, D. K. & Fishman, M. C. Impaired defense of intestinal mucosa in mice lacking intestinal trefoil factor. Science 274, 262–265 (1996)

    ADS  CAS  PubMed  Google Scholar 

  39. McVay, L. D. et al. Absence of bacterially induced RELMβ reduces injury in the dextran sodium sulfate model of colitis. J. Clin. Invest. 116, 2914–2923 (2006)

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Van der Sluis, M. et al. Muc2-deficient mice spontaneously develop colitis, indicating that MUC2 is critical for colonic protection. Gastroenterology 131, 117–129 (2006)

    CAS  PubMed  Google Scholar 

  41. An, G. et al. Increased susceptibility to colitis and colorectal tumors in mice lacking core 3-derived O-glycans. J. Exp. Med. 204, 1417–1429 (2007)

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Itoh, H., Beck, P. L., Inoue, N., Xavier, R. & Podolsky, D. K. A paradoxical reduction in susceptibility to colonic injury upon targeted transgenic ablation of goblet cells. J. Clin. Invest. 104, 1539–1547 (1999)

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Salzman, N. H., Underwood, M. A. & Bevins, C. L. Paneth cells, defensins, and the commensal microbiota: A hypothesis on intimate interplay at the intestinal mucosa. Semin. Immunol. 19, 70–83 (2007)

    CAS  PubMed  Google Scholar 

  44. Coombes, J. L. & Maloy, K. J. Control of intestinal homeostasis by regulatory T cells and dendritic cells. Semin. Immunol. 19, 116–126 (2007)

    CAS  PubMed  Google Scholar 

  45. Chieppa, M., Rescigno, M., Huang, A. Y. & Germain, R. N. Dynamic imaging of dendritic cell extension into the small bowel lumen in response to epithelial cell TLR engagement. J. Exp. Med. 203, 2841–2852 (2006)

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Niess, J. H. et al. CX3CR1-mediated dendritic cell access to the intestinal lumen and bacterial clearance. Science 307, 254–258 (2005)

    ADS  CAS  PubMed  Google Scholar 

  47. Becker, C. et al. Constitutive p40 promoter activation and IL-23 production in the terminal ileum mediated by dendritic cells. J. Clin. Invest. 112, 693–706 (2003)

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Hue, S. et al. Interleukin-23 drives innate and T cell-mediated intestinal inflammation. J. Exp. Med. 203, 2473–2483 (2006)

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Mizoguchi, A. et al. Dependence of intestinal granuloma formation on unique myeloid DC-like cells. J. Clin. Invest. 117, 605–615 (2007)

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Smith, P. D., Ochsenbauer-Jambor, C. & Smythies, L. E. Intestinal macrophages: unique effector cells of the innate immune system. Immunol. Rev. 206, 149–159 (2005)

    CAS  PubMed  Google Scholar 

  51. Takeda, K. et al. Enhanced Th1 activity and development of chronic enterocolitis in mice devoid of Stat3 in macrophages and neutrophils. Immunity 10, 39–49 (1999)

    CAS  PubMed  Google Scholar 

  52. Kamada, N. et al. Abnormally differentiated subsets of intestinal macrophage play a key role in Th1-dominant chronic colitis through excess production of IL-12 and IL-23 in response to bacteria. J. Immunol. 175, 6900–6908 (2005)

    CAS  PubMed  Google Scholar 

  53. Fort, M. M., Leach, M. W. & Rennick, D. M. A role for NK cells as regulators of CD4+ T cells in a transfer model of colitis. J. Immunol. 161, 3256–3261 (1998)

    CAS  PubMed  Google Scholar 

  54. Watanabe, T. et al. Nucleotide binding oligomerization domain 2 deficiency leads to dysregulated TLR2 signaling and induction of antigen-specific colitis. Immunity 25, 473–485 (2006)

    CAS  PubMed  Google Scholar 

  55. Franchimont, D. et al. Deficient host-bacteria interactions in inflammatory bowel disease? The toll-like receptor (TLR)-4 Asp299gly polymorphism is associated with Crohn's disease and ulcerative colitis. Gut 53, 987–992 (2004)

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Pierik, M. et al. Toll-like receptor-1, -2, and -6 polymorphisms influence disease extension in inflammatory bowel diseases. Inflamm. Bowel Dis. 12, 1–8 (2006)

    PubMed  Google Scholar 

  57. Torok, H. P. et al. Crohn's disease is associated with a toll-like receptor-9 polymorphism. Gastroenterology 127, 365–366 (2004)

    PubMed  Google Scholar 

  58. Inohara, N., Chamaillard, M., McDonald, C. & Nunez, G. NOD-LRR proteins: role in host–microbial interactions and inflammatory disease. Annu. Rev. Biochem. 74, 355–383 (2005)

    CAS  PubMed  Google Scholar 

  59. Kobayashi, K. et al. RICK/Rip2/CARDIAK mediates signalling for receptors of the innate and adaptive immune systems. Nature 416, 194–199 (2002)

    ADS  CAS  PubMed  Google Scholar 

  60. Barnich, N. et al. GRIM-19 interacts with nucleotide oligomerization domain 2 and serves as downstream effector of anti-bacterial function in intestinal epithelial cells. J. Biol. Chem. 280, 19021–19026 (2005)

    CAS  PubMed  Google Scholar 

  61. Chen, C. M., Gong, Y., Zhang, M. & Chen, J. J. Reciprocal cross-talk between Nod2 and TAK1 signaling pathways. J. Biol. Chem. 279, 25876–25882 (2004)

    CAS  PubMed  Google Scholar 

  62. Mayor, A., Martinon, F., De Smedt, T., Petrilli, V. & Tschopp, J. A crucial function of SGT1 and HSP90 in inflammasome activity links mammalian and plant innate immune responses. Nature Immunol. 8, 497–503 (2007)

    CAS  Google Scholar 

  63. McDonald, C. et al. A role for Erbin in the regulation of Nod2-dependent NF-κB signaling. J. Biol. Chem. 280, 40301–40309 (2005)

    CAS  PubMed  Google Scholar 

  64. Pan, Q. et al. NF-κB-inducing kinase regulates selected gene expression in the Nod2 signaling pathway. Infect. Immun. 74, 2121–2127 (2006)

    CAS  PubMed  PubMed Central  Google Scholar 

  65. da Silva Correia, J., Miranda, Y., Leonard, N. & Ulevitch, R. SGT1 is essential for Nod1 activation. Proc. Natl Acad. Sci. USA 104, 6764–6769 (2007)

    ADS  PubMed  PubMed Central  Google Scholar 

  66. Bruey, J. M. et al. Bcl-2 and Bcl-XL regulate proinflammatory caspase-1 activation by interaction with NALP1. Cell 129, 45–56 (2007)

    CAS  PubMed  Google Scholar 

  67. Kobayashi, K. S. et al. Nod2-dependent regulation of innate and adaptive immunity in the intestinal tract. Science 307, 731–734 (2005)

    ADS  CAS  PubMed  Google Scholar 

  68. Li, J. et al. Regulation of IL-8 and IL-1β expression in Crohn's disease associated NOD2/CARD15 mutations. Hum. Mol. Genet. 13, 1715–1725 (2004)

    CAS  PubMed  Google Scholar 

  69. Maeda, S. et al. Nod2 mutation in Crohn's disease potentiates NF-κB activity and IL-1β processing. Science 307, 734–738 (2005)

    ADS  CAS  PubMed  Google Scholar 

  70. Gutierrez, M. G. et al. Protective role of autophagy against Vibrio cholerae cytolysin, a pore-forming toxin from V. cholerae. Proc. Natl Acad. Sci. USA 104, 1829–1834 (2007)

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  71. Mizushima, N. & Klionsky, D. J. Protein Turnover Via Autophagy: Implications for Metabolism. Annu. Rev. Nutr. 27 doi: 10.1146/annurev.nutr.27.061406.093749 (2007)

  72. Ogawa, M. et al. Escape of intracellular Shigella from autophagy. Science 307, 727–731 (2005)

    ADS  CAS  PubMed  Google Scholar 

  73. Parkes, M. et al. Sequence variants in the autophagy gene IRGM and multiple other replicating loci contribute to Crohn's disease susceptibility. Nature Genet. 39, 830–832 (2007)

    CAS  PubMed  Google Scholar 

  74. Singh, S. B., Davis, A. S., Taylor, G. A. & Deretic, V. Human IRGM induces autophagy to eliminate intracellular mycobacteria. Science 313, 1438–1441 (2006)

    ADS  CAS  PubMed  Google Scholar 

  75. Taylor, G. A. IRG proteins: key mediators of interferon-regulated host resistance to intracellular pathogens. Cell. Microbiol. 9, 1099–1107 (2007)

    CAS  PubMed  Google Scholar 

  76. Ellson, C. D. et al. Neutrophils from p40phox-/- mice exhibit severe defects in NADPH oxidase regulation and oxidant-dependent bacterial killing. J. Exp. Med. 203, 1927–1937 (2006)

    CAS  PubMed  PubMed Central  Google Scholar 

  77. Matute, J. D., Arias, A. A., Dinauer, M. C. & Patino, P. J. p40phox: the last NADPH oxidase subunit. Blood Cells Mol. Dis. 35, 291–302 (2005)

    CAS  PubMed  Google Scholar 

  78. Stuart, L. M. & Ezekowitz, R. A. Phagocytosis: elegant complexity. Immunity 22, 539–550 (2005)

    CAS  PubMed  Google Scholar 

  79. Mosmann, T. R., Cherwinski, H., Bond, M. W., Giedlin, M. A. & Coffman, R. L. Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J. Immunol. 136, 2348–2357 (1986)

    CAS  PubMed  Google Scholar 

  80. Murphy, K. M. Fate vs choice: the immune system reloaded. Immunol. Res. 32, 193–200 (2005)

    MathSciNet  CAS  PubMed  Google Scholar 

  81. Weaver, C. T., Hatton, R. D., Mangan, P. R. & Harrington, L. E. IL-17 family cytokines and the expanding diversity of effector T cell lineages. Annu. Rev. Immunol. 25, 851–852 (2007)

    Google Scholar 

  82. Kastelein, R. A., Hunter, C. A. & Cua, D. J. Discovery and biology of IL-23 and IL-27: related but functionally distinct regulators of inflammation. Annu. Rev. Immunol. 25, 221–242 (2007)

    CAS  PubMed  Google Scholar 

  83. Bettelli, E., Oukka, M. & Kuchroo, V. K. TH-17 cells in the circle of immunity and autoimmunity. Nature Immunol. 8, 345–350 (2007)

    CAS  Google Scholar 

  84. Laurence, A. et al. Interleukin-2 signaling via STAT5 constrains T helper 17 cell generation. Immunity 26, 371–381 (2007)

    CAS  PubMed  Google Scholar 

  85. Ivanov, I. I. et al. The orphan nuclear receptor RORγt directs the differentiation program of proinflammatory IL-17+ T helper cells. Cell 126, 1121–1133 (2006)

    CAS  PubMed  Google Scholar 

  86. Schnurr, M. et al. Extracellular nucleotide signaling by P2 receptors inhibits IL-12 and enhances IL-23 expression in human dendritic cells: a novel role for the cAMP pathway. Blood 105, 1582–1589 (2005)

    CAS  PubMed  Google Scholar 

  87. Kullberg, M. C. et al. IL-23 plays a key role in Helicobacter hepaticus-induced T cell-dependent colitis. J. Exp. Med. 203, 2485–2494 (2006)

    CAS  PubMed  PubMed Central  Google Scholar 

  88. Uhlig, H. H. et al. Differential activity of IL-12 and IL-23 in mucosal and systemic innate immune pathology. Immunity 25, 309–318 (2006)

    CAS  PubMed  Google Scholar 

  89. Yen, D. et al. IL-23 is essential for T cell-mediated colitis and promotes inflammation via IL-17 and IL-6. J. Clin. Invest. 116, 1310–1316 (2006)

    CAS  PubMed  PubMed Central  Google Scholar 

  90. Kinugasa, T., Sakaguchi, T., Gu, X. & Reinecker, H. C. Claudins regulate the intestinal barrier in response to immune mediators. Gastroenterology 118, 1001–1011 (2000)

    CAS  PubMed  Google Scholar 

  91. Izcue, A., Coombes, J. L. & Powrie, F. Regulatory T cells suppress systemic and mucosal immune activation to control intestinal inflammation. Immunol. Rev. 212, 256–271 (2006)

    CAS  PubMed  Google Scholar 

  92. Akbar, A. N., Vukmanovic-Stejic, M., Taams, L. S. & Macallan, D. C. The dynamic co-evolution of memory and regulatory CD4+ T cells in the periphery. Nature Rev. Immunol. 7, 231–237 (2007)

    CAS  Google Scholar 

  93. Kim, J. M. & Rudensky, A. The role of the transcription factor Foxp3 in the development of regulatory T cells. Immunol. Rev. 212, 86–98 (2006)

    CAS  PubMed  Google Scholar 

  94. Yu, Q. T. et al. Expression and functional characterization of FOXP3+CD4+ regulatory T cells in ulcerative colitis. Inflamm. Bowel Dis. 168, 1898–1909 (2006)

    Google Scholar 

  95. Allez, M., Brimnes, J., Dotan, I. & Mayer, L. Expansion of CD8+ T cells with regulatory function after interaction with intestinal epithelial cells. Gastroenterology 123, 1516–1526 (2002)

    PubMed  Google Scholar 

  96. Mizoguchi, A. & Bhan, A. K. A case for regulatory B cells. J. Immunol. 176, 705–710 (2006)

    CAS  PubMed  Google Scholar 

  97. Fuss, I. J. et al. Nonclassical CD1d-restricted NK T cells that produce IL-13 characterize an atypical Th2 response in ulcerative colitis. J. Clin. Invest. 113, 1490–1497 (2004)

    CAS  PubMed  PubMed Central  Google Scholar 

  98. Ley, R. E., Peterson, D. A. & Gordon, J. I. Ecological and evolutionary forces shaping microbial diversity in the human intestine. Cell 124, 837–848 (2006)

    CAS  PubMed  Google Scholar 

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Acknowledgements

This work is supported by grants from the NIH (to R.J.X. and D.K.P.).

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  1. Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, and,,

    R. J. Xavier & D. K. Podolsky

  2. Center for Computational and Integrative Biology Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA,

    R. J. Xavier

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Xavier, R., Podolsky, D. Unravelling the pathogenesis of inflammatory bowel disease. Nature 448, 427–434 (2007). https://doi.org/10.1038/nature06005

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