Interleukin 20
receptors
Receptor may refer to:
*Sensory receptor, in physiology, any structure which, on receiving environmental stimuli, produces an informative nerve impulse
*Receptor (biochemistry), in biochemistry, a protein molecule that receives and responds to a n ...
(IL20R) belong to the
IL-10 family
The IL10 family is a family of interleukins.
In addition to IL-10, it includes IL-19, IL-20, IL-22, IL-24 and IL-26.
Some sources also include the interferons IL-28 and IL-29.
The IL-10 family are helical cytokines categorized based on ...
. IL20R are involved in both
pro-inflammatory
Inflammation (from la, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants, and is a protective response involving immune cells, blood vessels, and molecu ...
and anti-inflammatory immune response.
There are two types of IL20R: Type I and Type II.
IL20R is found in many organ resident
effector cell
In cell biology, an effector cell is any of various types of cell that actively responds to a stimulus and effects some change (brings it about).
Examples of effector cells include:
* The muscle, gland or organ cell capable of responding to ...
s such as
keratinocyte
Keratinocytes are the primary type of cell found in the epidermis, the outermost layer of the skin. In humans, they constitute 90% of epidermal skin cells.
Basal cells in the basal layer (''stratum basale'') of the skin are sometimes referre ...
s at the
skin epidermis,
osteoclast
An osteoclast () is a type of bone cell that breaks down bone tissue. This function is critical in the maintenance, repair, and remodeling of bones of the vertebral skeleton. The osteoclast disassembles and digests the composite of hydrated pro ...
s, found in bones, and
epithelial cells
Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercell ...
of the
intestine and
trachea
The trachea, also known as the windpipe, is a cartilaginous tube that connects the larynx to the bronchi of the lungs, allowing the passage of air, and so is present in almost all air- breathing animals with lungs. The trachea extends from the ...
. IL20R alpha and beta subunits have also been found in some immune cells.
IL20R is implicated in diseases such as
psoriasis
Psoriasis is a long-lasting, noncontagious autoimmune disease characterized by raised areas of abnormal skin. These areas are red, pink, or purple, dry, itchy, and scaly. Psoriasis varies in severity from small, localized patches to complete ...
,
rheumatoid arthritis
Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and hands are invol ...
, and
glaucoma
Glaucoma is a group of eye diseases that result in damage to the optic nerve (or retina) and cause vision loss. The most common type is open-angle (wide angle, chronic simple) glaucoma, in which the drainage angle for fluid within the eye rem ...
. Â
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.
Both types of receptor bind the
cytokine
Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in autocrin ...
s
IL-20,
IL-24. Type 1 also binds cytokine
IL-19.
Signaling
IL20R signalling happens through the
JAK-STAT pathway
The JAK-STAT signaling pathway is a chain of interactions between proteins in a cell, and is involved in processes such as immunity, cell division, cell death, and tumour formation. The pathway communicates information from chemical signals out ...
.
When an IL-20 subfamily cytokine binds IL20R, JAK's linked to intracellular domains of IL20R activate and
phosphorylate
In chemistry, phosphorylation is the attachment of a phosphate group to a molecule or an ion. This process and its inverse, dephosphorylation, are common in biology and could be driven by natural selection. Text was copied from this source, ...
tyrosine
-Tyrosine or tyrosine (symbol Tyr or Y) or 4-hydroxyphenylalanine is one of the 20 standard amino acids that are used by cells to synthesize proteins. It is a non-essential amino acid with a polar side group. The word "tyrosine" is from the G ...
residues found in the longer
alpha chain
The term alpha chain is normally used to indicate one of the subunits of a multi-subunit protein. The term "chain" is a general term given to any peptide sequence. It can often refer more specifically to mean:
* a part of the T-cell receptor,
* ...
s in the intracellular portion of the receptor.
STAT
STAT, Stat. , or stat may refer to:
* Stat (system call), a Unix system call that returns file attributes of an inode
* ''Stat'' (TV series), an American sitcom that aired in 1991
* Stat (website), a health-oriented news website
* STAT protein, a ...
then binds to docking sites created by JAK phosphorylation, and become phosphorylated by JAK's themselves. STATs then
dimerize
A dimer () ('' di-'', "two" + ''-mer'', "parts") is an oligomer consisting of two monomers joined by bonds that can be either strong or weak, covalent or intermolecular. Dimers also have significant implications in polymer chemistry, inorganic ch ...
and move to the
nucleus
Nucleus ( : nuclei) is a Latin word for the seed inside a fruit. It most often refers to:
*Atomic nucleus, the very dense central region of an atom
* Cell nucleus, a central organelle of a eukaryotic cell, containing most of the cell's DNA
Nucl ...
to act as
transcription factor
In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The f ...
s. 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.
STAT3 is the main transcription factor activated with IL20R signaling.
The Immune System and Link to Disease
IL20R subunit gene
mutation
In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA replication, DNA or viral repl ...
s and differences in gene expression are associated with an increased risk of
inflammatory diseases
Inflammation (from la, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants, and is a protective response involving immune cells, blood vessels, and molecu ...
.
IL20R and Psoriasis
IL20R has is involved in skin
homeostasis
In biology, homeostasis (British also homoeostasis) (/hɒmɪə(ʊ)ˈsteɪsɪs/) is the state of steady internal, physical, and chemical conditions maintained by living systems. This is the condition of optimal functioning for the organism and ...
. Research shows that IL-20R may play a role in the immune disease
psoriasis
Psoriasis is a long-lasting, noncontagious autoimmune disease characterized by raised areas of abnormal skin. These areas are red, pink, or purple, dry, itchy, and scaly. Psoriasis varies in severity from small, localized patches to complete ...
, where rapid growth of skin cells leads to dryness and irritation.
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
The T helper cells (Th cells), also known as CD4+ cells or CD4-positive cells, are a type of T cell that play an important role in the adaptive immune system. They aid the activity of other immune cells by releasing cytokines. They are consider ...
, 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.
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.
Research also shows that certain gene mutations in IL20R are associated with an increased risk of juvenile idiopathic arthritis.
Glaucoma
Research indicates that IL20Rs, specifically the IL20R beta subunit (IL20RB), may be linked with
glaucoma
Glaucoma is a group of eye diseases that result in damage to the optic nerve (or retina) and cause vision loss. The most common type is open-angle (wide angle, chronic simple) glaucoma, in which the drainage angle for fluid within the eye rem ...
, a disease that can lead to
blindness
Visual impairment, also known as vision impairment, is a medical definition primarily measured based on an individual's better eye visual acuity; in the absence of treatment such as correctable eyewear, assistive devices, and medical treatment†...
. 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
Intraocular pressure (IOP) is the fluid pressure inside the eye. Tonometry is the method eye care professionals use to determine this. IOP is an important aspect in the evaluation of patients at risk of glaucoma. Most tonometers are calibrated t ...
.
References
External links
*
{{Interleukin receptor modulators
Type II cytokine receptors