KEGG   PATHWAY: nvs05321
Entry
nvs05321                    Pathway                                
Name
Inflammatory bowel disease - Neogale vison (American mink)
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
nvs05321  Inflammatory bowel disease
nvs05321

Organism
Neogale vison (American mink) [GN:nvs]
Gene
122889469  TLR2; toll-like receptor 2 [KO:K10159]
122917312  TLR4; toll-like receptor 4 [KO:K10160]
122918706  TLR5; toll-like receptor 5 [KO:K10168]
122889330  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
122913121  RELA; transcription factor p65 [KO:K04735]
122911461  NOD2; nucleotide-binding oligomerization domain-containing protein 2 isoform X1 [KO:K10165]
122904655  LOW QUALITY PROTEIN: HLA class II histocompatibility antigen, DR alpha chain [KO:K06752]
122904716  H-2 class II histocompatibility antigen, E-S beta chain-like [KO:K06752]
122911007  HLA class II histocompatibility antigen, DP beta 1 chain-like isoform X1 [KO:K06752]
122911034  RLA class II histocompatibility antigen, DP alpha-1 chain [KO:K06752]
122911086  HLA class II histocompatibility antigen, DO alpha chain isoform X1 [KO:K06752]
122911149  HLA class II histocompatibility antigen, DM alpha chain isoform X1 [KO:K06752]
122911160  HLA class II histocompatibility antigen, DM beta chain isoform X1 [KO:K06752]
122911197  HLA class II histocompatibility antigen, DO beta chain [KO:K06752]
122911212  HLA class II histocompatibility antigen, DQ beta 1 chain isoform X1 [KO:K06752]
122911237  HLA class II histocompatibility antigen, DQ alpha 2 chain-like [KO:K06752]
122911244  SLA class II histocompatibility antigen, DQ haplotype D alpha chain-like [KO:K06752]
122911252  DLA class II histocompatibility antigen, DR-1 beta chain [KO:K06752]
122911259  HLA class II histocompatibility antigen, DR alpha chain [KO:K06752]
122894561  uncharacterized protein LOC122894561 [KO:K10784]
122891375  IFNG; interferon gamma [KO:K04687]
122906241  IFNGR1; interferon gamma receptor 1 [KO:K05132]
122908329  IFNGR2; interferon gamma receptor 2 isoform X1 [KO:K05133]
122902129  STAT1; signal transducer and activator of transcription 1-alpha/beta [KO:K11220]
122907735  TBX21; T-box transcription factor TBX21 [KO:K10166]
122901601  IL4; interleukin-4 [KO:K05430]
122901633  IL5; interleukin-5 [KO:K05428]
122910459  IL12A; interleukin-12 subunit alpha [KO:K05406]
122901988  IL12B; interleukin-12 subunit beta [KO:K05425]
122900068  IL12RB2; interleukin-12 receptor subunit beta-2 [KO:K05064]
122910727  IL12RB1; interleukin-12 receptor subunit beta-1 isoform X1 [KO:K05063]
122902130  STAT4; signal transducer and activator of transcription 4 [KO:K11222]
122890130  IL2; interleukin-2 [KO:K05429]
122912284  IL18; interleukin-18 [KO:K05482]
122893710  LOW QUALITY PROTEIN: interleukin-18-like [KO:K05482]
122916399  IL18R1; interleukin-18 receptor 1 [KO:K05173]
122915672  interleukin-18 receptor accessory protein [KO:K05174]
122900023  JUN; transcription factor AP-1 [KO:K04448]
122899945  TNF; tumor necrosis factor isoform X1 [KO:K03156]
122904064  IL6; interleukin-6 [KO:K05405]
122915761  IL1A; interleukin-1 alpha [KO:K04383]
122915760  IL1B; interleukin-1 beta [KO:K04519]
122912064  TGFB1; transforming growth factor beta-1 proprotein isoform X1 [KO:K13375]
122918428  TGFB2; transforming growth factor beta-2 proprotein isoform X1 [KO:K13376]
122893231  TGFB3; transforming growth factor beta-3 proprotein [KO:K13377]
122902898  SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
122894006  SMAD3; mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
122906196  STAT3; signal transducer and activator of transcription 3 isoform X1 [KO:K04692]
122890127  IL21; interleukin-21 [KO:K05434]
122895818  IL21R; interleukin-21 receptor isoform X1 [KO:K05075]
122892295  IL23A; interleukin-23 subunit alpha isoform X1 [KO:K05426]
122898731  IL23R; interleukin-23 receptor [KO:K05065]
122900521  RORC; nuclear receptor ROR-gamma isoform X1 [KO:K08534]
122892976  RORA; nuclear receptor ROR-alpha [KO:K08532]
122897069  FOXP3; forkhead box protein P3 [KO:K10163]
122899698  IL17A; interleukin-17A [KO:K05489]
122899705  IL17F; interleukin-17F [KO:K05494]
122891967  IL22; interleukin-22 [KO:K05445]
122895383  IL4R; interleukin-4 receptor subunit alpha isoform X1 [KO:K05071]
122896347  IL2RG; cytokine receptor common subunit gamma [KO:K05070]
122891094  STAT6; signal transducer and activator of transcription 6 isoform X1 [KO:K11225]
122890841  GATA3; trans-acting T-cell-specific transcription factor GATA-3 isoform X1 [KO:K17895]
122918166  IL10; interleukin-10 [KO:K05443]
122901617  IL13; LOW QUALITY PROTEIN: interleukin-13 [KO:K05435]
122911214  MAF; LOW QUALITY PROTEIN: transcription factor Maf [KO:K09035]
122902796  NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 isoform X1 [KO:K04446]
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
nvs04060  Cytokine-cytokine receptor interaction
nvs04612  Antigen processing and presentation
nvs04620  Toll-like receptor signaling pathway
nvs04621  NOD-like receptor signaling pathway
nvs04630  JAK-STAT signaling pathway
nvs04659  Th17 cell differentiation
nvs04660  T cell receptor signaling pathway
KO pathway
ko05321   
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