Interleukin-20 receptor

Last updated
interleukin 20 receptor, alpha
Identifiers
Symbol IL20RA
Alt. symbolsZCYTOR7, IL-20R1
NCBI gene 53832
HGNC 6003
OMIM 605620
RefSeq NM_014432
UniProt Q9UHF4
Other data
Locus Chr. 6 q23.3
Search for
Structures Swiss-model
Domains InterPro
interleukin 20 receptor beta
Identifiers
Symbol IL20RB
Alt. symbolsFNDC6
NCBI gene 53833
HGNC 6004
OMIM 605621
RefSeq NM_144717
UniProt Q6UXL0
Other data
Locus Chr. 3 q22.3
Search for
Structures Swiss-model
Domains InterPro

Interleukin 20 receptors (IL20R) belong to the IL-10 family. IL20R are involved in both pro-inflammatory and anti-inflammatory immune response. [1] [2] There are two types of IL20R: Type I and Type II.

Contents

IL20R is found in many organ resident effector cells such as keratinocytes at the skin epidermis, osteoclasts, found in bones, and epithelial cells of the intestine and trachea. IL20R alpha and beta subunits have also been found in some immune cells. [2] IL20R is implicated in diseases such as psoriasis, rheumatoid arthritis, and glaucoma.  

Structure and function

There are two types of IL20R: Type I, made up of the IL-20 receptor alpha subunit and beta subunit, and Type II, made up of the IL-22 receptor and IL-20 receptor beta subunit. [3] Both types of receptor bind the cytokines IL-20, IL-24. Type 1 also binds cytokine IL-19. [4] [5]

Signaling

IL20R signalling happens through the JAK-STAT pathway. [4] When an IL-20 subfamily cytokine binds IL20R, JAK's linked to intracellular domains of IL20R activate and phosphorylate tyrosine residues found in the longer alpha chains in the intracellular portion of the receptor. STAT then binds to docking sites created by JAK phosphorylation, and become phosphorylated by JAK's themselves. STATs then dimerize and move to the nucleus to act as transcription factors. The specific genes expressed are dependent on the specific JAK, STAT, as well as by SOCS proteins, which inhibit the JAK-STAT signal to regulate it. [3]

STAT3 is the main transcription factor activated with IL20R signaling. [6]

IL20R subunit gene mutations and differences in gene expression are associated with an increased risk of inflammatory diseases. [2]

IL20R and Psoriasis

IL20R has is involved in skin homeostasis. Research shows that IL-20R may play a role in the immune disease psoriasis, where rapid growth of skin cells leads to dryness and irritation. [3] Mutations in IL20R are associated with an increased risk of psoriasis, and psoriatic skin lesions show elevated levels of IL20R.

Under the current understanding of psoriasis, the over-activation of dendritic cells and macrophages leads to pro-inflammatory cytokine release, including TNFα and IL-23. This cytokine release activates T-helper cells, which produce cytokines IL-17 and IL-22, and subsequently leads to the release of IL-19 IL-20, and IL-24. The binding of IL-20, IL-24, and IL-19 to IL20R, along with other cytokines binding to their respective receptors, leads to high amounts of keratinocytes. The keratinocytes then lead to psoriatic plaque formation. [3]

Rheumatoid arthritis

IL20R is linked with rheumatoid arthritis, an autoimmune condition where the immune system attacks joints and other body areas and leads to pain. Elevated levels of IL20R mRNA and proteins are found in people with rheumatoid arthritis. It is thought that production of IL20 which binds to IL20Rs increases the production of chemoattractants, which are immune signaling molecules that can recruit immune cells. The chemoattractants then attract neutrophils and T-cells, which drive inflammation in the joints and cause pain. [3]

Research also shows that certain gene mutations in IL20R are associated with an increased risk of juvenile idiopathic arthritis. [2]

Glaucoma

Research indicates that IL20Rs, specifically the IL20R beta subunit (IL20RB), may be linked with glaucoma, a disease that can lead to blindness. It’s not believed that IL20RB has a causative effect on the disease, but it may contribute to an increased risk of the disease, along with other factors, such as intraocular pressure. [7]

Related Research Articles

<span class="mw-page-title-main">Interleukin 12</span> Interleukin

Interleukin 12 (IL-12) is an interleukin that is naturally produced by dendritic cells, macrophages, neutrophils, and human B-lymphoblastoid cells (NC-37) in response to antigenic stimulation. IL-12 belongs to the family of interleukin-12. IL-12 family is unique in comprising the only heterodimeric cytokines, which includes IL-12, IL-23, IL-27 and IL-35. Despite sharing many structural features and molecular partners, they mediate surprisingly diverse functional effects.

<span class="mw-page-title-main">Interleukin 15</span> Cytokine with structural similarity to Interleukin-2

Interleukin-15 (IL-15) is a protein that in humans is encoded by the IL15 gene. IL-15 is an inflammatory cytokine with structural similarity to Interleukin-2 (IL-2). Like IL-2, IL-15 binds to and signals through a complex composed of IL-2/IL-15 receptor beta chain (CD122) and the common gamma chain. IL-15 is secreted by mononuclear phagocytes following infection by virus(es). This cytokine induces the proliferation of natural killer cells, i.e. cells of the innate immune system whose principal role is to kill virally infected cells.

<span class="mw-page-title-main">Interleukin 31</span>

Interleukin-31 (IL-31) is a protein that in humans is encoded by the IL31 gene that resides on chromosome 12. IL-31 is an inflammatory cytokine that helps trigger cell-mediated immunity against pathogens. It has also been identified as a major player in a number of chronic inflammatory diseases, including atopic dermatitis.

<span class="mw-page-title-main">Interleukin 29</span> Protein-coding gene in the species Homo sapiens

Interleukin-29 (IL-29) is a cytokine and it belongs to type III interferons group, also termed interferons λ (IFN-λ). IL-29 plays an important role in the immune response against pathogenes and especially against viruses by mechanisms similar to type I interferons, but targeting primarily cells of epithelial origin and hepatocytes.

Interleukin 27 (IL-27) is a member of the IL-12 cytokine family. It is a heterodimeric cytokine that is encoded by two distinct genes, Epstein-Barr virus-induced gene 3 (EBI3) and IL-27p28. IL-27 is expressed by antigen presenting cells and interacts with a specific cell-surface receptor complex known as IL-27 receptor (IL-27R). This receptor consists of two proteins, IL-27Rɑ and gp130. IL-27 induces differentiation of the diverse populations of T cells in the immune system and also upregulates IL-10.

<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 protein that in humans is encoded by the IL22 gene.

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

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. IL-20 is a part of an IL-20 subfamily which is a part of a larger IL-10 family.

<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.

<span class="mw-page-title-main">Tyrosine kinase 2</span> Enzyme and coding gene in humans

Non-receptor tyrosine-protein kinase TYK2 is an enzyme that in humans is encoded by the TYK2 gene.

<span class="mw-page-title-main">Janus kinase 3</span> Mammalian protein found in Homo sapiens

Tyrosine-protein kinase JAK3 is a tyrosine kinase enzyme that in humans is encoded by the JAK3 gene.

<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-28 receptor is a type II cytokine receptor found largely in epithelial cells. It binds type 3 interferons, interleukin-28 A, Interleukin-28B, interleukin 29 and interferon lambda 4. It consists of an α chain and shares a common β subunit with the interleukin-10 receptor. Binding to the interleukin-28 receptor, which is restricted to select cell types, is important for fighting infection. Binding of the type 3 interferons to the receptor results in activation of the JAK/STAT signaling pathway.

<span class="mw-page-title-main">IL2RA</span> Mammalian protein found in Homo sapiens

Interleukin-2 receptor alpha chain is a protein involved in assembly of high-affinity Interleukin-2 receptor, consisting of alpha (IL2RA), beta (IL2RB) and the common gamma chain (IL2RG). As the name indicates, this receptor interacts with pleiotropic cytokine called Interleukin-2, which effect is mainly important for immune homeostasis.

<span class="mw-page-title-main">Interleukin-1 family</span> Group of cytokines playing a key role in the regulation of immune and inflammatory responses

The Interleukin-1 family is a group of 11 cytokines that plays a central role in the regulation of immune and inflammatory responses to infections or sterile insults.

<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.

Interleukin 36, or IL-36, is a group of cytokines in the IL-1 family with pro-inflammatory effects. The role of IL-36 in inflammatory diseases is under investigation.

<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.

References

  1. ↑ 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.
  2. 1 2 3 4 Kragstrup TW, Andersen T, Heftdal LD, Hvid M, Gerwien J, Sivakumar P, et al. (2018-09-25). "The IL-20 Cytokine Family in Rheumatoid Arthritis and Spondyloarthritis". Frontiers in Immunology. 9: 2226. doi: 10.3389/fimmu.2018.02226 . PMC   6167463 . PMID   30319661.
  3. 1 2 3 4 5 Wegenka UM (October 2010). "IL-20: biological functions mediated through two types of receptor complexes". Cytokine & Growth Factor Reviews. IL-10 Family of Cytokines. 21 (5): 353–363. doi:10.1016/j.cytogfr.2010.08.001. PMID   20864382.
  4. 1 2 Chen J, Caspi RR, Chong WP (November 2018). "IL-20 receptor cytokines in autoimmune diseases". Journal of Leukocyte Biology. 104 (5): 953–959. doi:10.1002/jlb.mr1117-471r. PMC   6298946 . PMID   30260500.
  5. ↑ Ouyang W, O'Garra A (April 2019). "IL-10 Family Cytokines IL-10 and IL-22: from Basic Science to Clinical Translation". Immunity. 50 (4): 871–891. doi: 10.1016/j.immuni.2019.03.020 . PMID   30995504. S2CID   122350808.
  6. ↑ Blumberg H, Conklin D, Xu WF, Grossmann A, Brender T, Carollo S, et al. (January 2001). "Interleukin 20: discovery, receptor identification, and role in epidermal function". Cell. 104 (1): 9–19. doi: 10.1016/S0092-8674(01)00187-8 . PMID   11163236. S2CID   7460710.
  7. ↑ Wirtz MK, Keller KE (2016). "The Role of the IL-20 Subfamily in Glaucoma". Mediators of Inflammation. 2016: 4083735. doi: 10.1155/2016/4083735 . PMC   4745377 . PMID   26903709.
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