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

external resources
NCBI:842771
KEGG:hsa05321
PUBMED:17499605
PUBMED:12006974
PUBMED:18053739
PUBMED:20134493
PUBMED:10898785
PUBMED:18563156
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PUBMED:18200661
PUBMED:12797537
PUBMED:21487504
PUBMED:19381306
PUBMED:21681604
PUBMED:19322214
PUBMED:16493424
PUBMED:18242222
PUBMED:12042806
PUBMED:9759857

genes
GATA3 , HLA-DMA , HLA-DMB , HLA-DOA , HLA-DOB , HLA-DPA1 , HLA-DPB1 , HLA-DQA1 , HLA-DQA2 , HLA-DQB1 , HLA-DRA , HLA-DRB1 , HLA-DRB5 , IFNG , IFNGR1 , IFNGR2 , IL1A , IL1B , IL2 , IL2RG , IL4 , IL4R , IL5 , IL6 , IL10 , IL12A , IL12B , IL12RB1 , IL12RB2 , IL13 , IL17A , IL18 , JUN , SMAD2 , SMAD3 , MAF , NFATC1 , NFKB1 , RELA , RORA , RORC , STAT1 , STAT3 , STAT4 , STAT6 , TGFB1 , TGFB2 , TGFB3 , TLR2 , TLR4 , TLR5 , TNF , IL18RAP , IL18R1 , TBX21 , IL21R , IL22 , FOXP3 , IL23A , IL21 , NOD2 , IL17F , IL23R ,