Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTKXIVNQ)

DOT Name	Interleukin-17C (IL17C)
Synonyms	IL-17C; Cytokine CX2
Gene Name	IL17C
Related Disease	Atopic dermatitis ( ) Autoimmune hepatitis ( ) Bipolar disorder ( ) Carcinoma ( ) Chronic obstructive pulmonary disease ( ) Crohn disease ( ) Dermatitis ( ) Epithelial neoplasm ( ) Hepatitis ( ) Hepatitis A virus infection ( ) Lung adenocarcinoma ( ) Lung cancer ( ) Lung carcinoma ( ) Lung squamous cell carcinoma ( ) Pneumonia ( ) Pneumonitis ( ) Psoriasis ( ) Ulcerative colitis ( ) Advanced cancer ( ) Colorectal carcinoma ( ) Immune system disorder ( ) Influenza ( ) Intestinal neoplasm ( ) Lung neoplasm ( ) Neoplasm ( ) Arthritis ( ) Inflammatory bowel disease ( ) Multiple sclerosis ( ) Nephropathy ( ) Periodontitis ( ) Type-1 diabetes ( )
UniProt ID	IL17C_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
Pfam ID	PF06083
Sequence	MTLLPGLLFLTWLHTCLAHHDPSLRGHPHSHGTPHCYSAEELPLGQAPPHLLARGAKWGQ ALPVALVSSLEAASHRGRHERPSATTQCPVLRPEEVLEADTHQRSISPWRYRVDTDEDRY PQKLAFAECLCRGCIDARTGRETAALNSVRLLQSLLVLRRRPCSRDGSGLPTPGAFAFHT EFIHVPVGCTCVLPRSV
Function	Cytokine that plays a crucial role in innate immunity of the epithelium, including to intestinal bacterial pathogens, in an autocrine manner. Stimulates the production of antibacterial peptides and pro-inflammatory molecules for host defense by signaling through the NF-kappa-B and MAPK pathways. Acts synergically with IL22 in inducing the expression of antibacterial peptides, including S100A8, S100A9, REG3A and REG3G. Synergy is also observed with TNF and IL1B in inducing DEFB2 from keratinocytes. Depending on the type of insult, may have both protective and pathogenic properties, either by maintaining epithelial homeostasis after an inflammatory challenge or by promoting inflammatory phenotype. Enhanced IL17C/IL17RE signaling may also lead to greater susceptibility to autoimmune diseases.
KEGG Pathway	Cytokine-cytokine receptor interaction (hsa04060 ) IL-17 sig.ling pathway (hsa04657 )
Reactome Pathway	Interleukin-17 signaling (R-HSA-448424 )

Molecular Interaction Atlas (MIA) of This DOT

31 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Atopic dermatitis	DISTCP41	Definitive	Biomarker	[1]
Autoimmune hepatitis	DISOX03Q	Strong	Biomarker	[2]
Bipolar disorder	DISAM7J2	Strong	Altered Expression	[3]
Carcinoma	DISH9F1N	Strong	Biomarker	[4]
Chronic obstructive pulmonary disease	DISQCIRF	Strong	Biomarker	[5]
Crohn disease	DIS2C5Q8	Strong	Biomarker	[6]
Dermatitis	DISY5SZC	Strong	Biomarker	[1]
Epithelial neoplasm	DIS0T594	Strong	Biomarker	[4]
Hepatitis	DISXXX35	Strong	Biomarker	[2]
Hepatitis A virus infection	DISUMFQV	Strong	Biomarker	[2]
Lung adenocarcinoma	DISD51WR	Strong	Altered Expression	[7]
Lung cancer	DISCM4YA	Strong	Biomarker	[7]
Lung carcinoma	DISTR26C	Strong	Biomarker	[7]
Lung squamous cell carcinoma	DISXPIBD	Strong	Altered Expression	[7]
Pneumonia	DIS8EF3M	Strong	Biomarker	[8]
Pneumonitis	DIS88E0K	Strong	Biomarker	[8]
Psoriasis	DIS59VMN	Strong	Biomarker	[1]
Ulcerative colitis	DIS8K27O	Strong	Biomarker	[9]
Advanced cancer	DISAT1Z9	moderate	Biomarker	[10]
Colorectal carcinoma	DIS5PYL0	moderate	Biomarker	[11]
Immune system disorder	DISAEGPH	moderate	Biomarker	[12]
Influenza	DIS3PNU3	moderate	Biomarker	[13]
Intestinal neoplasm	DISK0GUH	moderate	Altered Expression	[10]
Lung neoplasm	DISVARNB	moderate	Biomarker	[13]
Neoplasm	DISZKGEW	moderate	Biomarker	[13]
Arthritis	DIST1YEL	Limited	Biomarker	[14]
Inflammatory bowel disease	DISGN23E	Limited	Altered Expression	[15]
Multiple sclerosis	DISB2WZI	Limited	Altered Expression	[16]
Nephropathy	DISXWP4P	Limited	Biomarker	[17]
Periodontitis	DISI9JOI	Limited	Biomarker	[18]
Type-1 diabetes	DIS7HLUB	Limited	Altered Expression	[19]
------------------------------------------------------------------------------------


⏷ Show the Full List of 31 Disease(s)

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Interleukin-17C (IL17C).	[20]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Interleukin-17C (IL17C).	[24]
------------------------------------------------------------------------------------

4 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Interleukin-17C (IL17C).	[21]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Interleukin-17C (IL17C).	[22]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Interleukin-17C (IL17C).	[23]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Interleukin-17C (IL17C).	[25]
------------------------------------------------------------------------------------

References

1	IL-17C amplifies epithelial inflammation in human psoriasis and atopic eczema.J Eur Acad Dermatol Venereol. 2020 Apr;34(4):800-809. doi: 10.1111/jdv.16126. Epub 2020 Jan 19.
2	IL-17C/IL-17RE Augments T Cell Function in Autoimmune Hepatitis.J Immunol. 2017 Jan 15;198(2):669-680. doi: 10.4049/jimmunol.1600977. Epub 2016 Dec 12.
3	Hippocampal synaptic pathology in schizophrenia, bipolar disorder and major depression: a study of complexin mRNAs.Mol Psychiatry. 2000 Jul;5(4):425-32. doi: 10.1038/sj.mp.4000741.
4	Comparative study of interleukin-17C (IL-17C) and IL-17D in large yellow croaker Larimichthys crocea reveals their similar but differential functional activity.Dev Comp Immunol. 2017 Nov;76:34-44. doi: 10.1016/j.dci.2017.05.014. Epub 2017 May 16.
5	Rhinovirus and Bacteria Synergistically Induce IL-17C Release from Human Airway Epithelial Cells To Promote Neutrophil Recruitment.J Immunol. 2019 Jan 1;202(1):160-170. doi: 10.4049/jimmunol.1800547. Epub 2018 Nov 30.
6	IL-36 sustains a proinflammatory self-amplifying loop with IL-17C in anti-TNF-induced psoriasiform skin lesions of patients with Crohn's disease.Inflamm Bowel Dis. 2014 Nov;20(11):1891-901. doi: 10.1097/MIB.0000000000000198.
7	Comprehensive genomic and prognostic analysis of the IL?7 family genes in lung cancer.Mol Med Rep. 2019 Jun;19(6):4906-4918. doi: 10.3892/mmr.2019.10164. Epub 2019 Apr 15.
8	Interleukin 17 Receptor E (IL-17RE) and IL-17C Mediate the Recruitment of Neutrophils during Acute Streptococcus pneumoniae Pneumonia.Infect Immun. 2019 Oct 18;87(11):e00329-19. doi: 10.1128/IAI.00329-19. Print 2019 Nov.
9	DNA methylation profile of genes involved in inflammation and autoimmunity in inflammatory bowel disease.Medicine (Baltimore). 2014 Dec;93(28):e309. doi: 10.1097/MD.0000000000000309.
10	Alterations in the microbiota drive interleukin-17C production from intestinal epithelial cells to promote tumorigenesis.Immunity. 2014 Jan 16;40(1):140-52. doi: 10.1016/j.immuni.2013.11.018. Epub 2014 Jan 9.
11	A randomized double-blind placebo-controlled trial of probiotics in post-surgical colorectal cancer.BMC Gastroenterol. 2019 Jul 24;19(1):131. doi: 10.1186/s12876-019-1047-4.
12	IL-17C Mitigates Murine Acute Graft-vs.-Host Disease by Promoting Intestinal Barrier Functions and Treg Differentiation.Front Immunol. 2018 Nov 26;9:2724. doi: 10.3389/fimmu.2018.02724. eCollection 2018.
13	IL-17C-mediated innate inflammation decreases the response to PD-1 blockade in a model of Kras-driven lung cancer.Sci Rep. 2019 Jul 17;9(1):10353. doi: 10.1038/s41598-019-46759-8.
14	IL-17B and IL-17C are associated with TNF-alpha production and contribute to the exacerbation of inflammatory arthritis.J Immunol. 2007 Nov 15;179(10):7128-36. doi: 10.4049/jimmunol.179.10.7128.
15	Intestinal neuroendocrine cells and goblet cells are mediators of IL-17A-amplified epithelial IL-17C production in human inflammatory bowel disease.Mucosal Immunol. 2015 Jul;8(4):943-58. doi: 10.1038/mi.2014.124. Epub 2014 Dec 10.
16	Gene-microarray analysis of multiple sclerosis lesions yields new targets validated in autoimmune encephalomyelitis.Nat Med. 2002 May;8(5):500-8. doi: 10.1038/nm0502-500.
17	IL-17C/IL-17 Receptor E Signaling in CD4(+) T Cells Promotes T(H)17 Cell-Driven Glomerular Inflammation.J Am Soc Nephrol. 2018 Apr;29(4):1210-1222. doi: 10.1681/ASN.2017090949. Epub 2018 Feb 26.
18	Epigenetic characteristics in inflammatory candidate genes in aggressive periodontitis.Hum Immunol. 2016 Jan;77(1):71-75. doi: 10.1016/j.humimm.2015.10.007. Epub 2015 Oct 21.
19	Intestinal Epithelial Cell Regulation of Adaptive Immune Dysfunction in Human Type 1 Diabetes.Front Immunol. 2017 Jan 10;7:679. doi: 10.3389/fimmu.2016.00679. eCollection 2016.
20	Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
21	Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
22	Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
23	Grape resveratrol increases serum adiponectin and downregulates inflammatory genes in peripheral blood mononuclear cells: a triple-blind, placebo-controlled, one-year clinical trial in patients with stable coronary artery disease. Cardiovasc Drugs Ther. 2013 Feb;27(1):37-48. doi: 10.1007/s10557-012-6427-8.
24	Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
25	Transcriptomic?pathway?and?benchmark dose analysis of Bisphenol A, Bisphenol S, Bisphenol F, and 3,3',5,5'-Tetrabromobisphenol A in H9 human embryonic stem cells. Toxicol In Vitro. 2021 Apr;72:105097. doi: 10.1016/j.tiv.2021.105097. Epub 2021 Jan 18.