Ulcerative colitis signaling (Homo sapiens)

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12APCMDPPGN1335148Luminal bacteria3, 4DNA LipopolysaccharidesFlagellinColon lumenMucosa Inflammation4Peptidoglycans3, 11NF-kappa-B2NLR signaling pathwayTNF-α TLR signaling pathway67DNA TH0 cellMHCIINFKB1NOD2TLR210, 143, 123, 103, 109Inhibition of IBDTGFB1IL13TGFB1IL10FOXP3NKT cellTreg cell9169, 16631, 12129, 153, 129, 15123, 1261, 12Ulcerative colitis Activated Th1 cellDNA?DNATh2 lymphocyte DNADNAIL-10NFATc1STAT6c-mafIL-13IL-4R subunit alphaJAK-STAT signaling pathwayIL-4IL-5GATA-3ycIL-4IFN-y Antigen


Description

Ulcerative colitis (UC) together with Crohn’s disease (CD) are both chronic inflammation disorders in the gastrointestinal (GI) tract, and subtypes of inflammatory bowel disease (IBD). This inflammatory response in the GI tract is a result of various environmental and genetic components, microorganisms, and an impaired immune system. Among those many factors, changes in the luminal environment of the colonic epithelial cells are crucial and remain to be precisely analyzed. This pathway only considered UC, in which certain pathogens are found in increased or decreased amounts, compared to healthy controls.

In the upper section of the pathway, it is shown that the toll-like receptors (TLRs) recognized the components derived from microbes, such as flagellin, peptidoglycan (PGN), and lipopolysaccharide. As depicted on the left, also nucleotide-binding oligomerization domain (NOD) proteins, and antigen-presenting cells (APCs) recognized those microbial molecules. Activation of the TLR signaling pathway drives the upregulation of NF-kappa-B and its corresponding inflammation reaction. At the same time, the APC regulates the shift of naïve T-cells into effector T-cells and (Th2) and natural killer (NKT) T-cells. UC is mainly dominated by the Th2-type inflammation and the corresponding production of IL-4, IL-5, IL-13 and IL-10.

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Bibliography

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  1. Seidelin JB, Coskun M, Kvist PH, Holm TL, Holgersen K, Nielsen OH; ''IL-33 promotes GATA-3 polarization of gut-derived T cells in experimental and ulcerative colitis.''; J Gastroenterol, 2015 PubMed Europe PMC Scholia
  2. Xu M, Tao J, Yang Y, Tan S, Liu H, Jiang J, Zheng F, Wu B; ''Ferroptosis involves in intestinal epithelial cell death in ulcerative colitis.''; Cell Death Dis, 2020 PubMed Europe PMC Scholia
  3. Geremia A, Biancheri P, Allan P, Corazza GR, Di Sabatino A; ''Innate and adaptive immunity in inflammatory bowel disease.''; Autoimmun Rev, 2014 PubMed Europe PMC Scholia
  4. Larabi A, Barnich N, Nguyen HTT; ''New insights into the interplay between autophagy, gut microbiota and inflammatory responses in IBD.''; Autophagy, 2020 PubMed Europe PMC Scholia
  5. Zhang SZ, Zhao XH, Zhang DC; ''Cellular and molecular immunopathogenesis of ulcerative colitis.''; Cell Mol Immunol, 2006 PubMed Europe PMC Scholia
  6. Ho IC, Glimcher LH; ''Transcription: tantalizing times for T cells.''; Cell, 2002 PubMed Europe PMC Scholia
  7. Cario E; ''Therapeutic impact of toll-like receptors on inflammatory bowel diseases: a multiple-edged sword.''; Inflamm Bowel Dis, 2008 PubMed Europe PMC Scholia
  8. Tatiya-Aphiradee N, Chatuphonprasert W, Jarukamjorn K; ''Immune response and inflammatory pathway of ulcerative colitis.''; J Basic Clin Physiol Pharmacol, 2018 PubMed Europe PMC Scholia
  9. ''''; , PubMed Europe PMC Scholia
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  11. Ordás I, Eckmann L, Talamini M, Baumgart DC, Sandborn WJ; ''Ulcerative colitis.''; Lancet, 2012 PubMed Europe PMC Scholia
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  16. Singh SP, Chand HS, Banerjee S, Agarwal H, Raizada V, Roy S, Sopori M; ''Acetylcholinesterase Inhibitor Pyridostigmine Bromide Attenuates Gut Pathology and Bacterial Dysbiosis in a Murine Model of Ulcerative Colitis.''; Dig Dis Sci, 2020 PubMed Europe PMC Scholia

History

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CompareRevisionActionTimeUserComment
129376view09:47, 27 March 2024MkutmonOntology Term : 'disease pathway' added !
128414view13:12, 4 February 2024EweitzOntology Term : 'ulcerative colitis' added !
128413view13:11, 4 February 2024EweitzUpgrade disease node
121476view19:05, 17 February 2022LeonieSieder
121436view13:24, 17 February 2022AnaRodriguesAdded references to several interactions
121424view11:46, 17 February 2022AnaRodriguesAdded references to several interactions
121419view11:14, 17 February 2022MyrtevandeberghI have added a reference for the interactions between STAT6 on all sides, between GATA-3 and IL-4,5,13 and between NKT cell and IL13
121413view11:00, 17 February 2022MyrtevandeberghI have added an (extra) reference between IL-4 and the complex and between the complex and STAT6, also between IL-13 and UC and IL-13 and the inhibition of activated Th1 cell
121411view10:45, 17 February 2022MyrtevandeberghI added a reference (7) for the interaction between IL-5 and IL-13 with UC
121409view10:18, 17 February 2022MyrtevandeberghI have added a source for the interaction between Il-4 and the upregulation of STAT6
121398view10:08, 17 February 2022MyrtevandeberghI have added literature (5) to the interaction between STAT-6 and GATA-3
121395view09:51, 17 February 2022MyrtevandeberghI have changed TNF to TNF-α
121389view09:36, 17 February 2022MyrtevandeberghModified description
121387view09:34, 17 February 2022AnaRodrigues
121373view17:37, 16 February 2022MyrtevandeberghModified description
121356view11:14, 16 February 2022SMBachmannLiterature added
121229view23:37, 12 February 2022EweitzModified title
121178view14:13, 10 February 2022Myrtevandebergh
121177view14:12, 10 February 2022AnaRodrigues
121176view14:07, 10 February 2022SMBachmannModified description
121175view14:07, 10 February 2022SMBachmannModified description
121173view14:06, 10 February 2022SMBachmannOntology Term : 'inflammatory bowel disease 26' added !
121171view13:14, 10 February 2022LeonieSieder
121170view13:08, 10 February 2022AnaRodrigues
121169view13:03, 10 February 2022LeonieSieder
121135view15:30, 9 February 2022LeonieSieder
121133view15:20, 9 February 2022SMBachmannNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
FOXP3GeneProductENSG00000049768 (Ensembl)
GATA-3ProteinP23771 (Uniprot-TrEMBL)
IFN-y ProteinP01579 (Uniprot-TrEMBL)
IL-10ProteinP22301 (Uniprot-TrEMBL)
IL-13ProteinP35225 (Uniprot-TrEMBL)
IL-4ProteinD4HNR6 (Uniprot-TrEMBL)
IL-4ProteinP05112 (Uniprot-TrEMBL)
IL-4R subunit alphaProteinH3BRH7 (Uniprot-TrEMBL)
IL-5ProteinP05113 (Uniprot-TrEMBL)
IL10GeneProductENSG00000136634 (Ensembl)
IL13GeneProductENSG00000169194 (Ensembl)
JAK-STAT signaling pathwayPathwayhsa04630 (KEGG Pathway)
MDPMetaboliteQ259464 (Wikidata)
MHCIIGeneProductENSG00000204257 (Ensembl)
NF-kappa-BProteinP19838 (Uniprot-TrEMBL)
NFATc1ProteinO95644 (Uniprot-TrEMBL)
NFKB1GeneProductENSG00000109320 (Ensembl)
NLR signaling pathwayPathwayhsa04621 (KEGG Pathway)
NOD2GeneProductENSG00000167207 (Ensembl)
PGNMetaboliteCHEBI:8005 (ChEBI)
STAT6ProteinP42226 (Uniprot-TrEMBL)
TGFB1GeneProductENSG00000105329 (Ensembl)
TLR signaling pathwayPathwayhsa04064 (KEGG Pathway)
TLR2GeneProductENSG00000137462 (Ensembl)
TNF-α GeneProductENSG00000232810 (Ensembl)
c-mafProteinO75444 (Uniprot-TrEMBL)
ycGeneProductENSG00000147168 (Ensembl)

Annotated Interactions

No annotated interactions

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