Interleukin 20

Last updated
IL20
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases IL20 , IL-20, IL10D, ZCYTO10, Interleukin 20
External IDs OMIM: 605619; MGI: 1890473; HomoloGene: 10286; GeneCards: IL20; OMA:IL20 - orthologs
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 Mb Chr 1: 130.83 – 130.84 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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]

Contents

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]

Related Research Articles

<span class="mw-page-title-main">Immunosuppressive drug</span> Drug that inhibits activity of immune system

Immunosuppressive drugs, also known as immunosuppressive agents, immunosuppressants and antirejection medications, are drugs that inhibit or prevent the activity of the immune system.

A TNF inhibitor is a pharmaceutical drug that suppresses the physiologic response to tumor necrosis factor (TNF), which is part of the inflammatory response. TNF is involved in autoimmune and immune-mediated disorders such as rheumatoid arthritis, ankylosing spondylitis, inflammatory bowel disease, psoriasis, hidradenitis suppurativa and refractory asthma, so TNF inhibitors may be used in their treatment. The important side effects of TNF inhibitors include lymphomas, infections, congestive heart failure, demyelinating disease, a lupus-like syndrome, induction of auto-antibodies, injection site reactions, and systemic side effects.

<span class="mw-page-title-main">Biological therapy for inflammatory bowel disease</span>

Biological therapy, the use of medications called biopharmaceuticals or biologics that are tailored to specifically target an immune or genetic mediator of disease, plays a major role in the treatment of inflammatory bowel disease. Even for diseases of unknown cause, molecules that are involved in the disease process have been identified, and can be targeted for biological therapy. Many of these molecules, which are mainly cytokines, are directly involved in the immune system. Biological therapy has found a niche in the management of cancer, autoimmune diseases, and diseases of unknown cause that result in symptoms due to immune related mechanisms.

<span class="mw-page-title-main">Interleukin 26</span>

Interleukin-26 (IL-26) is a protein that in humans is encoded by the IL26 gene.

<span class="mw-page-title-main">Interleukin 24</span> Protein-coding gene in the species Homo sapiens

Interleukin 24 (IL-24) is a protein in the interleukin family, a type of cytokine signaling molecule in the immune system. In humans, this protein is encoded by the IL24 gene.

<span class="mw-page-title-main">Interleukin 22</span> Protein, encoded in humans by IL22 gene

Interleukin-22 (IL-22) is a protein that in humans is encoded by the IL22 gene.

<span class="mw-page-title-main">Interleukin 17</span> Group of proteins

Interleukin 17 family is a family of pro-inflammatory cystine knot cytokines. They are produced by a group of T helper cell known as T helper 17 cell in response to their stimulation with IL-23. Originally, Th17 was identified in 1993 by Rouvier et al. who isolated IL17A transcript from a rodent T-cell hybridoma. The protein encoded by IL17A is a founding member of IL-17 family. IL17A protein exhibits a high homology with a viral IL-17-like protein encoded in the genome of T-lymphotropic rhadinovirus Herpesvirus saimiri. In rodents, IL-17A is often referred to as CTLA8.

T helper 17 cells (Th17) are a subset of pro-inflammatory T helper cells defined by their production of interleukin 17 (IL-17). They are related to T regulatory cells and the signals that cause Th17s to actually inhibit Treg differentiation. However, Th17s are developmentally distinct from Th1 and Th2 lineages. Th17 cells play an important role in maintaining mucosal barriers and contributing to pathogen clearance at mucosal surfaces; such protective and non-pathogenic Th17 cells have been termed as Treg17 cells.

<span class="mw-page-title-main">Interleukin 20 receptor, alpha subunit</span> Protein-coding gene in the species Homo sapiens

Interleukin 20 receptor, alpha subunit, is a subunit of the interleukin-20 receptor, the interleukin-26 receptor, and the interleukin-24 receptor. The interleukin 20 receptor, alpha subunit is also referred to as IL20R1 or IL20RA. The IL20RA receptor is involved in both pro-inflammatory and anti-inflammatory responses, signaling through the JAK-STAT pathway.

<span class="mw-page-title-main">Interleukin 20 receptor, beta subunit</span> Protein-coding gene in the species Homo sapiens

Interleukin 20 receptor, beta subunit is a subunit of the interleukin-20 receptor and interleukin-22 receptor. It is believed to be involved in both pro-inflammatory and anti-inflammatory responses.

Interleukin 20 receptors (IL20R) belong to the IL-10 family. IL20R are involved in both pro-inflammatory and anti-inflammatory immune response. There are two types of IL20R: Type I and Type II.

<span class="mw-page-title-main">Interleukin-17A</span> Protein-coding gene in the species Homo sapiens

Interleukin-17A is a protein that in humans is encoded by the IL17A gene. In rodents, IL-17A used to be referred to as CTLA8, after the similarity with a viral gene.

<span class="mw-page-title-main">Interleukin-17 receptor</span> Type of protein receptor

Interleukin-17 receptor (IL-17R) is a cytokine receptor which belongs to new subfamily of receptors binding proinflammatory cytokine interleukin 17A, a member of IL-17 family ligands produced by T helper 17 cells (Th17). IL-17R family consists of 5 members: IL-17RA, IL-17RB, IL-17RC, IL-17RD and IL-17RE. Functional IL-17R is a transmembrane receptor complex usually consisting of one IL-17RA, which is a founding member of the family, and second other family subunit, thus forming heteromeric receptor binding different ligands. IL-17A, a founding member of IL-17 ligand family binds to heteromeric IL-17RA/RC receptor complex. IL-17RB binds preferentially IL-17B and IL-17E and heteromeric IL-17RA/RE complex binds IL-17C. However, there is still unknown ligand for IL-17RD. The first identified member IL-17RA is located on human chromosome 22, whereas other subunits IL-17RB to IL-17RD are encoded within human chromosome 3.

The IL-10 family is a family of interleukins.

<span class="mw-page-title-main">Secukinumab</span> Monoclonal antibody against IL-17

Secukinumab, sold under the brand name Cosentyx among others, is a human IgG1κ monoclonal antibody used for the treatment of psoriasis, ankylosing spondylitis, and psoriatic arthritis. It binds to the protein interleukin (IL)-17A and is marketed by Novartis.

<span class="mw-page-title-main">Interleukin 23</span> Heterodimeric cytokine acting as mediator of inflammation

Interleukin 23 (IL-23) is a heterodimeric cytokine composed of an IL-12B (IL-12p40) subunit and an IL-23A (IL-23p19) subunit. IL-23 is part of the IL-12 family of cytokines. The functional receptor for IL-23 consists of a heterodimer between IL-12Rβ1 and IL-23R.

Otilimab is a fully human antibody which has been developed by the biotechnology company MorphoSys. It can also be referred to as HuCAL antibody, HuCAL standing for Human Combinatorial Antibody Library and being a technology used to generate monoclonal antibodies. Otilimab is directed against the granulocyte-macrophage colony stimulating factor (GM-CSF), a monomeric glycoprotein functioning as a cytokine promoting both proliferation and activation of macrophages and neutrophils.

<span class="mw-page-title-main">Interleukin 17F</span>

Interleukin 17F (IL-17F) is signaling protein that is in human is encoded by the IL17F gene and is considered a pro-inflammatory cytokine. This protein belongs to the interleukin 17 family and is mainly produced by the T helper 17 cells after their stimulation with interleukin 23. However, IL-17F can be also produced by a wide range of cell types, including innate immune cells and epithelial cells.

Th22 cells are subpopulation of CD4+ T cells that produce interleukin-22 (IL-22). They play a role in the protective mechanisms against variety of bacterial pathogens, tissue repair and wound healing, and also in pathologic processes, including inflammations, autoimmunity, tumors, and digestive organs damages.

<span class="mw-page-title-main">Interleukin 40</span> Mammalian cytokine

Interleukin 40 (IL-40), also known with other name C17orf99, is a protein belonging to a group of cytokines called interleukins. It is encoded by a gene that does not belong to any cytokine superfamily. This cytokine is produced primarily by human expression tissues such as bone marrow and fetal liver, and its expression can be also induced in peripheral B cells after activation. IL-40 is involved in immunoglobulin A (IgA) production, and plays an important role in humoral immune responses and B cell homeostasis and development.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000162891 – Ensembl, May 2017
  2. 1 2 3 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. 1 2 3 4 5 6 7 8 9 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. 1 2 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. 1 2 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 (inactive 2024-09-17). PMC   4788924 . PMID   26968800.{{cite journal}}: CS1 maint: DOI inactive as of September 2024 (link)
  11. 1 2 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. 1 2 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. 1 2 3 4 5 6 7 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. 1 2 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. 1 2 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.

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