Interleukin 20

receptors Receptor may refer to: *Sensory receptor, in physiology, any neurite structure that, on receiving environmental stimuli, produces an informative nerve impulse *Receptor (biochemistry), in biochemistry, a protein molecule that receives and responds ...

(IL20R) belong to the

IL-10 family The IL-10 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 ) is part of the biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. The five cardinal signs are heat, pain, redness, swelling, and loss of function (Latin ''calor'', ''d ...

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 bone remodeling, remodeling of bones of the vertebrate, vertebral skeleton. The osteoclast disassembles and digests th ...

s, found in bones, and

epithelial cells Epithelium or epithelial tissue is a thin, continuous, protective layer of cells with little extracellular matrix. An example is the epidermis, the outermost layer of the skin. Epithelial ( mesothelial) tissues line the outer surfaces of man ...

of the

intestine The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The tract is the largest of the body's systems, after the cardiovascular system. T ...

and

trachea The trachea (: tracheae or tracheas), 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 animals' lungs. The trachea extends from ...

. 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 patches of abnormal skin. These areas are red, pink, or purple, dry, itchy, and scaly. Psoriasis varies in severity from small localized patches to complete b ...

rheumatoid arthritis Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects synovial joint, joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and h ...

, and

glaucoma Glaucoma is a group of eye diseases that can lead to damage of the optic nerve. The optic nerve transmits visual information from the eye to the brain. Glaucoma may cause vision loss if left untreated. It has been called the "silent thief of ...

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 produced by a broad range of cells, including immune cells like macrophages, B cell, B lymphocytes, T cell, T lymphocytes ...

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 tumor formation. The pathway communicates information from chemical signals outs ...

. When an IL-20 subfamily cytokine binds IL20R, JAK's linked to intracellular domains of IL20R activate and

phosphorylate In biochemistry, phosphorylation is described as the "transfer of a phosphate group" from a donor to an acceptor. A common phosphorylating agent (phosphate donor) is ATP and a common family of acceptor are alcohols: : This equation can be writt ...

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 conditionally essential amino acid with a polar side group. The word "tyrosine" is ...

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 then binds to docking sites created by JAK phosphorylation, and become phosphorylated by JAK's themselves. STATs then

dimerize In chemistry, dimerization is the process of joining two identical or similar Molecular entity, molecular entities by Chemical bond, bonds. The resulting bonds can be either strong or weak. Many symmetrical chemical species are described as dim ...

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 Nucleu ...

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 (genetics), transcription of genetics, genetic information from DNA to messenger RNA, by binding t ...

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 or viral replication, ...

s and differences in gene expression are associated with an increased risk of

inflammatory diseases Inflammation (from ) is part of the biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or Irritation, irritants. The five cardinal signs are heat, pain, redness, swelling, and Functio laesa, loss of funct ...

IL20R and Psoriasis

IL20R has is involved in skin

homeostasis In biology, homeostasis (British English, British also homoeostasis; ) is the state of steady internal physics, physical and chemistry, chemical conditions maintained by organism, living systems. This is the condition of optimal functioning fo ...

. Research shows that IL-20R may play a role in the immune disease

, 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 cell A dendritic cell (DC) is an antigen-presenting cell (also known as an ''accessory cell'') of the mammalian immune system. A DC's main function is to process antigen material and present it on the cell surface to the T cells of the immune system ...

s and

macrophage Macrophages (; abbreviated MPhi, φ, MΦ or MP) are a type of white blood cell of the innate immune system that engulf and digest pathogens, such as cancer cells, microbes, cellular debris and foreign substances, which do not have proteins that ...

s leads to pro-inflammatory cytokine release, including

TNFα Tumor necrosis factor (TNF), formerly known as TNF-α, is a chemical messenger produced by the immune system that induces inflammation. TNF is produced primarily by activated macrophages, and induces inflammation by binding to its receptors o ...

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 considere ...

, 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

, a disease that can lead to

blindness Visual or vision impairment (VI or VIP) is the partial or total inability of visual perception. In the absence of treatment such as corrective eyewear, assistive devices, and medical treatment, visual impairment may cause the individual difficul ...

. 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