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Entry
map05321                    Pathway                                

Name
Inflammatory bowel disease (IBD)
Description
Inflammatory bowel disease (IBD), which includes Crohn disease (CD) and ulcerative colitis (UC), is characterized by chronic inflammation of the gastrointestinal tract due to environmental and genetic factors, infectious microbes, and the dysregulated immune system. Although many environmental factors (for example, geographic locations, smoking, etc.) affect the development of IBD, the most crucial might be the luminal (external) environment of the epithelial cells. There are pathogens that are found in increasing frequency in IBD. The microbial components such as flagellin, peptidoglycan, and lipopolysaccharide are recognized by receptors such as toll-like receptors (TLRs) and nucleotide-binding oligomerization domain (NOD) proteins, and also by antigen-presenting cells (APCs) in genetically susceptible host. The TLR recognition triggers the activation of NF-kappaB, leading to an inflammatory response. APC-expressed gene NOD2 has been associated with Crohn disease. In case of mutations of NOD2, negative regulation of IL-12 production is reduced with the stimulation of muramyl dipeptide (MDP), leading to CD. In addition, the APC mediates the differentiation of naive T cells into effector T cells (Th1, Th17, Th2) and natural killer T (NKT) cells. Th1 and Th17 cells produce high levels of IFN-gamma and IL-17, -22, respectively, both of which promote CD. In contrast, Th2 cells produce IL-4, -5, -10, which together with IL-13 from NKT induce UC.
Class
Human Diseases; Immune diseases
BRITE hierarchy
Pathway map
map05321  Inflammatory bowel disease (IBD)
map05321

Ortholog table
Disease
H00286  Crohn disease
H01227  Inflammatory bowel disease (IBD)
H01466  Ulcerative colitis
H01971  IPEX syndrome
Reference
  Authors
Melmed GY, Targan SR
  Title
Future biologic targets for IBD: potentials and pitfalls.
  Journal
Nat Rev Gastroenterol Hepatol 7:110-7 (2010)
DOI:10.1038/nrgastro.2009.218
Reference
  Authors
Shih DQ, Targan SR
  Title
Immunopathogenesis of inflammatory bowel disease.
  Journal
World J Gastroenterol 14:390-400 (2008)
DOI:10.3748/wjg.14.390
Reference
  Authors
Baumgart DC, Carding SR
  Title
Inflammatory bowel disease: cause and immunobiology.
  Journal
Lancet 369:1627-40 (2007)
DOI:10.1016/S0140-6736(07)60750-8
Reference
  Authors
Strober W, Murray PJ, Kitani A, Watanabe T
  Title
Signalling pathways and molecular interactions of NOD1 and NOD2.
  Journal
Nat Rev Immunol 6:9-20 (2006)
DOI:10.1038/nri1747
Reference
  Authors
Matricon J, Barnich N, Ardid D
  Title
Immunopathogenesis of inflammatory bowel disease.
  Journal
Self Nonself 1:299-309 (2010)
DOI:10.4161/self.1.4.13560
Reference
  Authors
Agnello D, Lankford CS, Bream J, Morinobu A, Gadina M, O'Shea JJ, Frucht DM
  Title
Cytokines and transcription factors that regulate T helper cell differentiation: new players and new insights.
  Journal
J Clin Immunol 23:147-61 (2003)
DOI:10.1023/A:1023381027062
Reference
  Authors
Glimcher LH, Murphy KM
  Title
Lineage commitment in the immune system: the T helper lymphocyte grows up.
  Journal
Genes Dev 14:1693-711 (2000)
DOI:10.1101/gad.14.14.1693
Reference
  Authors
Neurath MF, Finotto S, Glimcher LH
  Title
The role of Th1/Th2 polarization in mucosal immunity.
  Journal
Nat Med 8:567-73 (2002)
DOI:10.1038/nm0602-567
Reference
  Authors
Afkarian M, Sedy JR, Yang J, Jacobson NG, Cereb N, Yang SY, Murphy TL, Murphy KM
  Title
T-bet is a STAT1-induced regulator of IL-12R expression in naive CD4+ T cells.
  Journal
Nat Immunol 3:549-57 (2002)
DOI:10.1038/ni794
Reference
  Authors
Sartor RB
  Title
Microbial influences in inflammatory bowel diseases.
  Journal
Gastroenterology 134:577-94 (2008)
DOI:10.1053/j.gastro.2007.11.059
Reference
PMID:9759857
  Authors
Yoshimoto T, Takeda K, Tanaka T, Ohkusu K, Kashiwamura S, Okamura H, Akira S, Nakanishi K
  Title
IL-12 up-regulates IL-18 receptor expression on T cells, Th1 cells, and B cells: synergism with IL-18 for IFN-gamma production.
  Journal
J Immunol 161:3400-7 (1998)
Reference
  Authors
Hur SJ, Kang SH, Jung HS, Kim SC, Jeon HS, Kim IH, Lee JD
  Title
Review of natural products actions on cytokines in inflammatory bowel disease.
  Journal
Nutr Res 32:801-16 (2012)
DOI:10.1016/j.nutres.2012.09.013
Reference
  Authors
Bettelli E, Korn T, Oukka M, Kuchroo VK
  Title
Induction and effector functions of T(H)17 cells.
  Journal
Nature 453:1051-7 (2008)
DOI:10.1038/nature07036
Reference
  Authors
Ivanov II, Zhou L, Littman DR
  Title
Transcriptional regulation of Th17 cell differentiation.
  Journal
Semin Immunol 19:409-17 (2007)
DOI:10.1016/j.smim.2007.10.011
Reference
  Authors
Di Cesare A, Di Meglio P, Nestle FO
  Title
The IL-23/Th17 axis in the immunopathogenesis of psoriasis.
  Journal
J Invest Dermatol 129:1339-50 (2009)
DOI:10.1038/jid.2009.59
Reference
  Authors
Jetten AM
  Title
Retinoid-related orphan receptors (RORs): critical roles in development, immunity, circadian rhythm, and cellular metabolism.
  Journal
Nucl Recept Signal 7:e003 (2009)
DOI:10.1621/nrs.07003
Reference
  Authors
Bene L, Falus A, Baffy N, Fulop AK
  Title
Cellular and molecular mechanisms in the two major forms of inflammatory bowel disease.
  Journal
Pathol Oncol Res 17:463-72 (2011)
DOI:10.1007/s12253-011-9397-4
KO pathway
ko05321   

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