KEGG   PATHWAY: ajm05321
Entry
ajm05321                    Pathway                                
Name
Inflammatory bowel disease - Artibeus jamaicensis (Jamaican fruit-eating bat)
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 disease
Pathway map
ajm05321  Inflammatory bowel disease
ajm05321

Disease
H01227  Inflammatory bowel disease (IBD)
Organism
Artibeus jamaicensis (Jamaican fruit-eating bat) [GN:ajm]
Gene
119035395  IL2RG; cytokine receptor common subunit gamma isoform X1 [KO:K05070]
119035652  STAT6; signal transducer and activator of transcription 6 isoform X1 [KO:K11225]
119035699  [KO:K06752]
119035735  IFNGR2; interferon gamma receptor 2 [KO:K05133]
119036537  TLR5; toll-like receptor 5 [KO:K10168]
119037587  IL21; interleukin-21 [KO:K05434]
119037638  IL2; interleukin-2 [KO:K05429]
119037707  IL4; interleukin-4 [KO:K05430]
119038537  [KO:K06752]
119040193  IL22; interleukin-22 [KO:K05445]
119040315  IL23A; interleukin-23 subunit alpha [KO:K05426]
119040794  [KO:K06752]
119042309  IFNG; interferon gamma [KO:K04687]
119042560  IL6; interleukin-6 isoform X1 [KO:K05405]
119045347  IL21R; interleukin-21 receptor isoform X1 [KO:K05075]
119045813  TGFB2; transforming growth factor beta-2 proprotein isoform X1 [KO:K13376]
119046462  NOD2; nucleotide-binding oligomerization domain-containing protein 2 isoform X3 [KO:K10165]
119046827  IL12RB1; interleukin-12 receptor subunit beta-1 isoform X1 [KO:K05063]
119047913  IL18RAP; interleukin-18 receptor accessory protein isoform X1 [KO:K05174]
119047914  IL18R1; interleukin-18 receptor 1 isoform X5 [KO:K05173]
119048122  RORC; nuclear receptor ROR-gamma [KO:K08534]
119048495  [KO:K10785]
119048496  [KO:K10785]
119048626  [KO:K06752]
119049266  TGFB3; transforming growth factor beta-3 proprotein [KO:K13377]
119050282  RELA; transcription factor p65 [KO:K04735]
119051373  NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 isoform X1 [KO:K04446]
119051654  JUN; transcription factor Jun [KO:K04448]
119051850  IFNGR1; interferon gamma receptor 1 [KO:K05132]
119052142  STAT3; signal transducer and activator of transcription 3 isoform X1 [KO:K04692]
119052666  TBX21; T-box transcription factor TBX21 [KO:K10166]
119052973  GATA3; trans-acting T-cell-specific transcription factor GATA-3 isoform X1 [KO:K17895]
119052984  [KO:K06752]
119052987  [KO:K06752]
119053473  RORA; nuclear receptor ROR-alpha isoform X1 [KO:K08532]
119053704  TNF; tumor necrosis factor isoform X1 [KO:K03156]
119054378  IL12B; interleukin-12 subunit beta [KO:K05425]
119055092  [KO:K05071]
119055693  [KO:K06752]
119056324  TLR4; toll-like receptor 4 isoform X1 [KO:K10160]
119056534  IL18; interleukin-18 [KO:K05482]
119056744  [KO:K06752]
119056745  [KO:K06752]
119056783  IL10; interleukin-10 [KO:K05443]
119057106  SMAD3; mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
119057921  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
119058462  TGFB1; transforming growth factor beta-1 proprotein [KO:K13375]
119059501  FOXP3; forkhead box protein P3 isoform X3 [KO:K10163]
119059740  IL17A; interleukin-17A isoform X2 [KO:K05489]
119059756  IL17F; interleukin-17F [KO:K05494]
119062087  [KO:K06752]
119062093  STAT1; signal transducer and activator of transcription 1-alpha/beta isoform X1 [KO:K11220]
119062106  STAT4; signal transducer and activator of transcription 4 isoform X1 [KO:K11222]
119063512  IL12RB2; interleukin-12 receptor subunit beta-2 isoform X1 [KO:K05064]
119063530  IL23R; interleukin-23 receptor [KO:K05065]
119063624  SMAD2; mothers against decapentaplegic homolog 2 [KO:K04500]
119065843  IL1A; interleukin-1 alpha [KO:K04383]
119065847  IL1B; interleukin-1 beta [KO:K04519]
119065905  TLR2; toll-like receptor 2 isoform X1 [KO:K10159]
128626235  IL12A; interleukin-12 subunit alpha isoform X1 [KO:K05406]
128627646  MAF; transcription factor Maf isoform X1 [KO:K09035]
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
Related
pathway
ajm04060  Cytokine-cytokine receptor interaction
ajm04612  Antigen processing and presentation
ajm04620  Toll-like receptor signaling pathway
ajm04621  NOD-like receptor signaling pathway
ajm04630  JAK-STAT signaling pathway
ajm04659  Th17 cell differentiation
ajm04660  T cell receptor signaling pathway
KO pathway
ko05321   

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