Immunopathogenesis of Inflammatory Bowel Disease

Overview

Journal Self Nonself

Specialty Allergy & Immunology

Date 2011 Apr 14

PMID 21487504

Citations 97

Authors

Julien Matricon

Nicolas Barnich

Denis Ardid

Affiliations

Soon will be listed here.

Abstract

Inflammatory bowel disease (IBD) is a group of idiopathic, chronic and relapsing inflammatory conditions of the gastrointestinal tract. Familial and epidemiological studies have stressed the involvement of genetic factors and have also shown the critical role of environmental factors such as sanitation and hygiene in the development of IBD. However, the molecular mechanisms of intestinal inflammation in IBD have long remained unknown. In recent years, the study of susceptibility genes involved in the detection of bacterial components and in the regulation of the host immune response has shed light onto the potential role of intestinal pathogens and gut flora in IBD immunobiology. This review presents current knowledge on intestinal epithelial barrier alterations and on dysfunction of mucosal innate and acquired immune responses in IBD. The data support the etiological hypothesis which argues that pathogenic intestinal bacteria and/or infectious agents initiate and perpetuate the inflammation of the gut through disruption of tolerance towards the commensal microbiota in an individual with genetic vulnerability.

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References

Hill K, Wang K, Stryker S, Gupta R, Weinrach D, Rao M . Comparative analysis of cell adhesion molecules, cell cycle regulatory proteins, mismatch repair genes, cyclooxygenase-2, and DPC4 in carcinomas arising in inflammatory bowel disease and sporadic colon cancer. Oncol Rep. 2004; 11(5):951-6. View

Wehkamp J, Harder J, Weichenthal M, Schwab M, Schaffeler E, Schlee M . NOD2 (CARD15) mutations in Crohn's disease are associated with diminished mucosal alpha-defensin expression. Gut. 2004; 53(11):1658-64. PMC: 1774270. DOI: 10.1136/gut.2003.032805. View

Baumgart D, Carding S . Inflammatory bowel disease: cause and immunobiology. Lancet. 2007; 369(9573):1627-40. DOI: 10.1016/S0140-6736(07)60750-8. View

Hugot J, Chamaillard M, Zouali H, Lesage S, Cezard J, Belaiche J . Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease. Nature. 2001; 411(6837):599-603. DOI: 10.1038/35079107. View

Maeda S, Hsu L, Liu H, Bankston L, Iimura M, Kagnoff M . Nod2 mutation in Crohn's disease potentiates NF-kappaB activity and IL-1beta processing. Science. 2005; 307(5710):734-8. DOI: 10.1126/science.1103685. View

Holstein A, Burmeister J, Plaschke A, Rosemeier D, Widjaja A, Egberts E . Autoantibody profiles in microscopic colitis. J Gastroenterol Hepatol. 2006; 21(6):1016-20. DOI: 10.1111/j.1440-1746.2005.04027.x. View

Cosnes J, Carbonnel F, Carrat F, Beaugerie L, Cattan S, Gendre J . Effects of current and former cigarette smoking on the clinical course of Crohn's disease. Aliment Pharmacol Ther. 1999; 13(11):1403-11. DOI: 10.1046/j.1365-2036.1999.00630.x. View

Targan S, Karp L . Defects in mucosal immunity leading to ulcerative colitis. Immunol Rev. 2005; 206:296-305. DOI: 10.1111/j.0105-2896.2005.00286.x. View

Baumgart M, Dogan B, Rishniw M, Weitzman G, Bosworth B, Yantiss R . Culture independent analysis of ileal mucosa reveals a selective increase in invasive Escherichia coli of novel phylogeny relative to depletion of Clostridiales in Crohn's disease involving the ileum. ISME J. 2007; 1(5):403-18. DOI: 10.1038/ismej.2007.52. View

10.

Fellermann K, Stange D, Schaeffeler E, Schmalzl H, Wehkamp J, Bevins C . A chromosome 8 gene-cluster polymorphism with low human beta-defensin 2 gene copy number predisposes to Crohn disease of the colon. Am J Hum Genet. 2006; 79(3):439-48. PMC: 1559531. DOI: 10.1086/505915. View

11.

Bettelli E, Carrier Y, Gao W, Korn T, Strom T, Oukka M . Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature. 2006; 441(7090):235-8. DOI: 10.1038/nature04753. View

12.

Tieng V, Le Bouguenec C, du Merle L, Bertheau P, Desreumaux P, Janin A . Binding of Escherichia coli adhesin AfaE to CD55 triggers cell-surface expression of the MHC class I-related molecule MICA. Proc Natl Acad Sci U S A. 2002; 99(5):2977-82. PMC: 122458. DOI: 10.1073/pnas.032668099. View

13.

Strober W, Fuss I, Mannon P . The fundamental basis of inflammatory bowel disease. J Clin Invest. 2007; 117(3):514-21. PMC: 1804356. DOI: 10.1172/JCI30587. View

14.

Eisenhauer P, Harwig S, Lehrer R . Cryptdins: antimicrobial defensins of the murine small intestine. Infect Immun. 1992; 60(9):3556-65. PMC: 257361. DOI: 10.1128/iai.60.9.3556-3565.1992. View

15.

Ito Y, Kanai T, Totsuka T, Okamoto R, Tsuchiya K, Nemoto Y . Blockade of NKG2D signaling prevents the development of murine CD4+ T cell-mediated colitis. Am J Physiol Gastrointest Liver Physiol. 2007; 294(1):G199-207. DOI: 10.1152/ajpgi.00286.2007. View

16.

Barnich N, Carvalho F, Glasser A, Darcha C, Jantscheff P, Allez M . CEACAM6 acts as a receptor for adherent-invasive E. coli, supporting ileal mucosa colonization in Crohn disease. J Clin Invest. 2007; 117(6):1566-74. PMC: 1868786. DOI: 10.1172/JCI30504. View

17.

Reuter B, Pizarro T . Mechanisms of tight junction dysregulation in the SAMP1/YitFc model of Crohn's disease-like ileitis. Ann N Y Acad Sci. 2009; 1165:301-7. DOI: 10.1111/j.1749-6632.2009.04035.x. View

18.

Takesue Y, Ohge H, Uemura K, Imamura Y, Murakami Y, Yokoyama T . Bacterial translocation in patients with Crohn's disease undergoing surgery. Dis Colon Rectum. 2002; 45(12):1665-71. DOI: 10.1007/s10350-004-7256-z. View

19.

Loftus Jr E . Clinical epidemiology of inflammatory bowel disease: Incidence, prevalence, and environmental influences. Gastroenterology. 2004; 126(6):1504-17. DOI: 10.1053/j.gastro.2004.01.063. View

20.

Simms L, Doecke J, Walsh M, Huang N, Fowler E, Radford-Smith G . Reduced alpha-defensin expression is associated with inflammation and not NOD2 mutation status in ileal Crohn's disease. Gut. 2008; 57(7):903-10. DOI: 10.1136/gut.2007.142588. View