Entry Name Inflammatory bowel disease
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 diseaseBRITE hierarchy
Pathway map Disease H01227 Inflammatory bowel disease (IBD)
Orthology K02580 NFKB1; nuclear factor NF-kappa-B p105 subunit
K03156 TNF, TNFA; tumor necrosis factor superfamily, member 2
K04383 IL1A; interleukin 1 alpha
K04446 NFATC1, NFAT2, NFATC; nuclear factor of activated T-cells, cytoplasmic 1
K04448 JUN; transcription factor AP-1
K04500 SMAD2; mothers against decapentaplegic homolog 2
K04519 IL1B; interleukin 1 beta
K04692 STAT3; signal transducer and activator of transcription 3
K04735 RELA; transcription factor p65
K05063 IL12RB1, CD212; interleukin 12 receptor beta-1
K05064 IL12RB2; interleukin 12 receptor beta-2
K05065 IL23R; interleukin 23 receptor
K05070 IL2RG, CD132; interleukin 2 receptor gamma
K05071 IL4R, CD124; interleukin 4 receptor
K05075 IL21R, CD360; interleukin 21 receptor
K05132 IFNGR1, CD119; interferon gamma receptor 1
K05133 IFNGR2; interferon gamma receptor 2
K05173 IL18R1, IL1RRP, CD218a; interleukin 18 receptor 1
K05174 IL18RAP, ACPL, CD218b; interleukin 18 receptor accessory protein
K05426 IL23A; interleukin 23 subunit alpha
K05443 IL10, CSIF; interleukin 10
K05445 IL22, IL-TIF; interleukin 22
K05482 IL18, IL1F4; interleukin 18
K05489 IL17A, CTLA8; interleukin 17A
K05494 IL17F, ML1; interleukin 17F
K06752 MHC2; MHC class II antigen
K08532 NR1F1, RORA; RAR-related orphan receptor alpha
K08534 NR1F3, RORC; RAR-related orphan receptor gamma
K09035 CMAF, MAF; transcription factor Maf
K10159 TLR2, CD282; toll-like receptor 2
K10160 TLR4, CD284; toll-like receptor 4
K10163 FOXP3, IPEX; forkhead box P3
K10165 NOD2, CARD15; nucleotide-binding oligomerization domain-containing protein 2
K10166 TBX21; T-box protein 21
K10168 TLR5; toll-like receptor 5
K10784 TRAV; T cell receptor alpha chain V region
K10785 TRBV; T-cell receptor beta chain V region
K11220 STAT1; signal transducer and activator of transcription 1
K11222 STAT4; signal transducer and activator of transcription 4
K11225 STAT6; signal transducer and activator of transcription 6
K13375 TGFB1; transforming growth factor beta-1
K13376 TGFB2; transforming growth factor beta-2
K13377 TGFB3; transforming growth factor beta-3
K17895 GATA3; GATA-binding protein 3
K23605 SMAD3; mothers against decapentaplegic homolog 3
Reference Authors Melmed GY, Targan SR
Title Future biologic targets for IBD: potentials and pitfalls.
Journal Reference Authors Shih DQ, Targan SR
Title Immunopathogenesis of inflammatory bowel disease.
Journal Reference Authors Baumgart DC, Carding SR
Title Inflammatory bowel disease: cause and immunobiology.
Journal Reference Authors Strober W, Murray PJ, Kitani A, Watanabe T
Title Signalling pathways and molecular interactions of NOD1 and NOD2.
Journal Reference Authors Matricon J, Barnich N, Ardid D
Title Immunopathogenesis of inflammatory bowel disease.
Journal 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 Reference Authors Glimcher LH, Murphy KM
Title Lineage commitment in the immune system: the T helper lymphocyte grows up.
Journal Reference Authors Neurath MF, Finotto S, Glimcher LH
Title The role of Th1/Th2 polarization in mucosal immunity.
Journal 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 Reference Authors Sartor RB
Title Microbial influences in inflammatory bowel diseases.
Journal Reference 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 Reference Authors Bettelli E, Korn T, Oukka M, Kuchroo VK
Title Induction and effector functions of T(H)17 cells.
Journal Reference Authors Ivanov II, Zhou L, Littman DR
Title Transcriptional regulation of Th17 cell differentiation.
Journal Reference Authors Di Cesare A, Di Meglio P, Nestle FO
Title The IL-23/Th17 axis in the immunopathogenesis of psoriasis.
Journal Reference Authors Jetten AM
Title Retinoid-related orphan receptors (RORs): critical roles in development, immunity, circadian rhythm, and cellular metabolism.
Journal 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 Related ko04060 Cytokine-cytokine receptor interaction
ko04612 Antigen processing and presentation
ko04620 Toll-like receptor signaling pathway
ko04621 NOD-like receptor signaling pathway
ko04660 T cell receptor signaling pathway
