Entry
Name
Inflammatory bowel disease - Mus musculus (house mouse)
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
BRITE hierarchy
Pathway map
Ortholog table
Organism
Mus musculus (house mouse) [GN:
mmu ]
Gene
18033 Nfkb1; nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105 [KO:K02580 ]
19697 Rela; v-rel reticuloendotheliosis viral oncogene homolog A (avian) [KO:K04735 ]
257632 Nod2; nucleotide-binding oligomerization domain containing 2 [KO:K10165 ]
14960 H2-Aa; histocompatibility 2, class II antigen A, alpha [KO:K06752 ]
14961 H2-Ab1; histocompatibility 2, class II antigen A, beta 1 [KO:K06752 ]
14969 H2-Eb1; histocompatibility 2, class II antigen E beta [KO:K06752 ]
14998 H2-DMa; histocompatibility 2, class II, locus DMa [KO:K06752 ]
14999 H2-DMb1; histocompatibility 2, class II, locus Mb1 [KO:K06752 ]
15000 H2-DMb2; histocompatibility 2, class II, locus Mb2 [KO:K06752 ]
15001 H2-Oa; histocompatibility 2, O region alpha locus [KO:K06752 ]
15002 H2-Ob; histocompatibility 2, O region beta locus [KO:K06752 ]
100504404 H2-Ea; histocompatibility 2, class II antigen E alpha [KO:K06752 ]
381091 H2-Eb2; histocompatibility 2, class II antigen E beta2 [KO:K06752 ]
20846 Stat1; signal transducer and activator of transcription 1 [KO:K11220 ]
16162 Il12rb2; interleukin 12 receptor, beta 2 [KO:K05064 ]
16161 Il12rb1; interleukin 12 receptor, beta 1 [KO:K05063 ]
20849 Stat4; signal transducer and activator of transcription 4 [KO:K11222 ]
16174 Il18rap; interleukin 18 receptor accessory protein [KO:K05174 ]
21803 Tgfb1; transforming growth factor, beta 1 [KO:K13375 ]
21808 Tgfb2; transforming growth factor, beta 2 [KO:K13376 ]
21809 Tgfb3; transforming growth factor, beta 3 [KO:K13377 ]
20848 Stat3; signal transducer and activator of transcription 3 [KO:K04692 ]
83430 Il23a; interleukin 23, alpha subunit p19 [KO:K05426 ]
19885 Rorc; RAR-related orphan receptor gamma [KO:K08534 ]
19883 Rora; RAR-related orphan receptor alpha [KO:K08532 ]
16186 Il2rg; interleukin 2 receptor, gamma chain [KO:K05070 ]
20852 Stat6; signal transducer and activator of transcription 6 [KO:K11225 ]
18018 Nfatc1; nuclear factor of activated T cells, cytoplasmic, calcineurin dependent 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 pathway
mmu04060 Cytokine-cytokine receptor interaction
mmu04612 Antigen processing and presentation
mmu04620 Toll-like receptor signaling pathway
mmu04621 NOD-like receptor signaling pathway
mmu04660 T cell receptor signaling pathway
KO pathway
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