Interleukin 20

Interleukin 20 (IL20) is a protein that is in humans encoded by the IL20 gene which is located in close proximity to the IL-10 gene on the 1q32 chromosome.[5][6] IL-20 is a part of an IL-20 subfamily which is a part of a larger IL-10 family.[5]

IL20
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesIL20, IL-20, IL10D, ZCYTO10, Interleukin 20
External IDsOMIM: 605619 MGI: 1890473 HomoloGene: 10286 GeneCards: IL20
Orthologs
SpeciesHumanMouse
Entrez

50604

58181

Ensembl

ENSG00000162891

ENSMUSG00000026416

UniProt

Q9NYY1

Q9JKV9

RefSeq (mRNA)

NM_018724

NM_021380
NM_001311091

RefSeq (protein)

NP_061194

NP_001298020
NP_067355

Location (UCSC)Chr 1: 206.87 – 206.87 MbChr 1: 130.83 – 130.84 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

IL-20 subfamily also includes other cytokines, including IL-19, IL-20, IL-22, IL-24, and IL-26.[5] Members of the cytokine IL-20 subfamily form an important link between the immune system and epithelial tissues due to the fact that receptors for these cytokines are highly expressed on epithelial cells and are almost exclusively produced by cells of the immune system.[7]

IL-20 requires an IL-β-subunit receptor (IL-20RB) for signaling, which can form a functional heterodimeric receptor with either the α-subunit of the IL-20 receptor (IL-20RA) or the α1-subunit of the IL-22 receptor (IL-22RA1). Both of these receptor variants allow efficient IL-20 signaling.[5] Receptors for IL-20 are expressed in the skin, lungs, ovary, testes, and placenta.[5] IL-20 is mainly produced by myeloid cells such as monocytes, granulocytes, and dendritic cells but can also be produced by keratinocytes and fibroblasts.[5] The expression of IL-20 is stimulated by IL-1β, IL-17, IL-22, TNF, and LPS.[5] The main cellular targets of IL-20 are keratinocytes, endothelial cells, and adipocytes.[8] IL-20 has been shown to transduce its signal through signal transducer and activator of transcription 3 (STAT3) in keratinocytes.[9]

Function

IL-20 has a broad range of functions and is involved in a variety of immune and non-immune processes in the body.[5] For example, IL-20 is involved in the process of wound healing, proliferation of epithelial cells, prevention of apoptosis of epithelial cells,[5] regulation of differentiation of keratinocytes during inflammation, the expansion of multipotential hematopoietic progenitor cells, and more.[10]

A specific receptor for this cytokine is highly upregulated in psoriatic skin.[6][11] Dysfunctional regulation of IL-20 could lead to uncontrollable wound healing in psoriasis, which could be a contributing factor to the pathogenesis of this disease.[11]

Because IL-20 is involved in the promotion of proliferation of epithelial cells it is also linked to the development of cancer. Receptors for IL-20 are very often expressed on tumorous cells of epithelial origin.[12] High expression of IL-20 is also associated with bladder cancer.[12] On the other hand, IL-20 is known to prevent tissue damage as a result of chronic inflammation which may reduce the chance of developing cancer. So the role of IL-20 in cancer development is ambiguous and needs to be further explored.[13]

IL-20 is an angiogenesis factor and is highly expressed in artery plaques found in patients with atherosclerosis.[14]

In rheumatoid arthritis

IL-20 is involved in many stages of rheumatoid arthritis (RA) progression.[15] IL-20 stimulates the secretion of chemokines MCP-1 and IL-8 in synovial fibroblasts, which attract neutrophils and T-cells.[16][17] IL-20 is also an upstream regulator of TNF-α, IL-1, and IL-6, which are involved in the pathogenesis of RA.[15] IL-20 is highly expressed in the synovial fluid of RA patients. Serum levels of IL-20 are not different from those of healthy controls, suggesting that IL-20 is involved in the pathogenesis of RA only at local sites of inflammation.[15] Receptors for IL-20 are highly expressed in the synovial membranes of RA patients.[15] Due to the clear association of IL-20 with RA, anti-IL-20 antibody is now in a clinical trial for RA.[15][18]

Antibody

Anti-IL-20 monoclonal antibodies have been researched as clinical candidates for the treatment or prevention of psoriasis, rheumatoid arthritis, atherosclerosis, osteoporosis, and stroke.[10][17][19] The anti-IL-20 antibody has been shown to reduce the severity of RA in rats, mitigate bone destruction, and more. The anti-IL-20 antibody neutralizes not only IL-20 signaling but also decreases TNF-α, IL-1, and IL-6 signaling in vivo.[15][18] A human recombinant monoclonal antibody against IL-20 developed by Novo Nordisk Inc. now entered the IIb phase of a clinical trial.[15]

References
  1. GRCh38: Ensembl release 89: ENSG00000162891 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000026416 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. Rutz S, Wang X, Ouyang W (December 2014). "The IL-20 subfamily of cytokines--from host defence to tissue homeostasis". Nature Reviews. Immunology. 14 (12): 783–795. doi:10.1038/nri3766. PMID 25421700. S2CID 29114703.
  6. Kontogiorgis CA, Hadjipavlou-Litina DJ (January 2002). "Non steroidal anti-inflammatory and anti-allergy agents". Current Medicinal Chemistry. 9 (1): 89–98. doi:10.2174/187152306778017683. PMID 11860351.
  7. Ouyang W, Rutz S, Crellin NK, Valdez PA, Hymowitz SG (2011-04-23). "Regulation and functions of the IL-10 family of cytokines in inflammation and disease". Annual Review of Immunology. 29 (1): 71–109. doi:10.1146/annurev-immunol-031210-101312. PMID 21166540.
  8. Sa SM, Valdez PA, Wu J, Jung K, Zhong F, Hall L, et al. (February 2007). "The effects of IL-20 subfamily cytokines on reconstituted human epidermis suggest potential roles in cutaneous innate defense and pathogenic adaptive immunity in psoriasis". Journal of Immunology. 178 (4): 2229–2240. doi:10.4049/jimmunol.178.4.2229. PMID 17277128. S2CID 1870754.
  9. "Entrez Gene: Interleukin 20".
  10. Kragstrup TW, Greisen SR, Nielsen MA, Rhodes C, Stengaard-Pedersen K, Hetland ML, et al. (March 2016). "The interleukin-20 receptor axis in early rheumatoid arthritis: novel links between disease-associated autoantibodies and radiographic progression". Arthritis Research & Therapy. 18 (1): 61. doi:10.1186/s13075-016-0964-7. PMC 4788924. PMID 26968800.
  11. Sano S, Chan KS, Carbajal S, Clifford J, Peavey M, Kiguchi K, et al. (January 2005). "Stat3 links activated keratinocytes and immunocytes required for development of psoriasis in a novel transgenic mouse model". Nature Medicine. 11 (1): 43–49. doi:10.1038/nm1162. PMID 15592573. S2CID 20474354.
  12. Lee SJ, Lee EJ, Kim SK, Jeong P, Cho YH, Yun SJ, et al. (2012-09-04). Frangogiannis N (ed.). "Identification of pro-inflammatory cytokines associated with muscle invasive bladder cancer; the roles of IL-5, IL-20, and IL-28A". PLOS ONE. 7 (9): e40267. Bibcode:2012PLoSO...740267L. doi:10.1371/journal.pone.0040267. PMC 3433484. PMID 22962576.
  13. Meira LB, Bugni JM, Green SL, Lee CW, Pang B, Borenshtein D, et al. (July 2008). "DNA damage induced by chronic inflammation contributes to colon carcinogenesis in mice". The Journal of Clinical Investigation. 118 (7): 2516–2525. doi:10.1172/JCI35073. PMC 2423313. PMID 18521188.
  14. Chen WY, Cheng BC, Jiang MJ, Hsieh MY, Chang MS (September 2006). "IL-20 is expressed in atherosclerosis plaques and promotes atherosclerosis in apolipoprotein E-deficient mice". Arteriosclerosis, Thrombosis, and Vascular Biology. 26 (9): 2090–2095. doi:10.1161/01.ATV.0000232502.88144.6f. PMID 16778121. S2CID 8237021.
  15. Hsu YH, Chang MS (June 2017). "IL-20 in rheumatoid arthritis". Drug Discovery Today. 22 (6): 960–964. doi:10.1016/j.drudis.2015.08.002. PMID 26297177.
  16. Hsu YH, Li HH, Hsieh MY, Liu MF, Huang KY, Chin LS, et al. (September 2006). "Function of interleukin-20 as a proinflammatory molecule in rheumatoid and experimental arthritis". Arthritis and Rheumatism. 54 (9): 2722–2733. doi:10.1002/art.22039. PMID 16947773.
  17. Kragstrup TW, Otkjaer K, Holm C, Jørgensen A, Hokland M, Iversen L, Deleuran B (January 2008). "The expression of IL-20 and IL-24 and their shared receptors are increased in rheumatoid arthritis and spondyloarthropathy" (PDF). Cytokine. 41 (1): 16–23. doi:10.1016/j.cyto.2007.10.004. PMID 18061474.
  18. Hsu YH, Chang MS (May 2014). "The therapeutic potential of anti-interleukin-20 monoclonal antibody". Cell Transplantation. 23 (4–5): 631–639. doi:10.3727/096368914X678319. PMID 24816455. S2CID 10729459.
  19. Hsu YH, Chen WY, Chan CH, Wu CH, Sun ZJ, Chang MS (August 2011). "Anti-IL-20 monoclonal antibody inhibits the differentiation of osteoclasts and protects against osteoporotic bone loss". The Journal of Experimental Medicine. 208 (9): 1849–1861. doi:10.1084/jem.20102234. PMC 3171097. PMID 21844205.
  • Overview of all the structural information available in the PDB for UniProt: Q9NYY1 (Interleukin-20) at the PDBe-KB.

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