Entry Name Inflammatory bowel disease - Miniopterus natalensis (Natal long-fingered 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 diseaseBRITE hierarchy
Pathway map Ortholog table Organism Miniopterus natalensis (Natal long-fingered bat) [GN:
mna ]
Gene 107545508 NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580 ]
107531027 NOD2; nucleotide-binding oligomerization domain-containing protein 2 [KO:K10165 ]
107545174 HLA class II histocompatibility antigen, DQ beta 1 chain-like [KO:K06752 ]
107536419 DLA class II histocompatibility antigen, DR-1 beta chain [KO:K06752 ]
107544122 HLA class II histocompatibility antigen, DR alpha chain [KO:K06752 ]
107542667 LOW QUALITY PROTEIN: HLA class II histocompatibility antigen, DP beta 1 chain [KO:K06752 ]
107542672 HLA class II histocompatibility antigen, DM alpha chain isoform X1 [KO:K06752 ]
107542674 HLA class II histocompatibility antigen, DM beta chain [KO:K06752 ]
107545091 HLA class II histocompatibility antigen, DQ beta 1 chain-like [KO:K06752 ]
107545092 SLA class II histocompatibility antigen, DQ haplotype D alpha chain-like [KO:K06752 ]
107540521 STAT1; signal transducer and activator of transcription 1-alpha/beta isoform X1 [KO:K11220 ]
107540906 STAT4; signal transducer and activator of transcription 4 [KO:K11222 ]
107546622 SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500 ]
107528938 STAT3; signal transducer and activator of transcription 3 isoform X1 [KO:K04692 ]
107532895 IL2RG; cytokine receptor common subunit gamma isoform X1 [KO:K05070 ]
107546227 STAT6; signal transducer and activator of transcription 6 isoform X1 [KO:K11225 ]
107542426 GATA3; trans-acting T-cell-specific transcription factor GATA-3 isoform X1 [KO:K17895 ]
107541561 NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 [KO:K04446 ]
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 mna04060 Cytokine-cytokine receptor interaction
mna04612 Antigen processing and presentation
mna04620 Toll-like receptor signaling pathway
mna04621 NOD-like receptor signaling pathway
mna04660 T cell receptor signaling pathway
KO pathway LinkDB All DBs
