Interleukin-28 receptor
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Interleukin-28 receptor is a
Structure
The interleukin 28 receptor consists of an interleukin-28R alpha chain (IL-28RA) and another receptor, the beta subunit of the Interleukin-10 receptor (IL-10R2).[7] IL-10R2 is part of the receptor for other cytokines such as IL-10, IL-22, IL-26,[5] and IL-20.[1] The IL-28Ra chain is a part of the cytokine receptor family 2.[5] The IL-28Ra chain is important for recognition and ligand specificity, while the IL-10R2 is crucial in signaling.[8]
Location
While the
Function
On binding of a type 3 interferon to the IL-28RA the IL-10RB is recruited leading to the activation of two
When the type 3 cytokines bind to the interleukin-28 receptor it causes several cellular responses that aid the skin cells in fighting infection. In binding to the receptor, interferon lambdas inhibit cell growth and the cell begins to produce cellular receptors that can sense infection as well as proteins to fight a viral infection. The interleukin-28 receptor, once a ligand is bound will activate a signaling pathway that causes an increase in
Regulation
Researchers have noted that IL-28RA gene expression is increased during stimulation by other interferons. There is also an increased expression of IL-28RA on the surface during maturation of monocytes to macrophages.[1] While the signaling cascade induced by type 3 interferons binding to their receptor results in significant protection from infections, the response must be regulated to prevent uncontrolled inflammation and apoptosis. Mechanisms involved in regulation can include induction of suppressor of cytokine signaling proteins (SOCSs).[1] There also exists a soluble splice variant of the receptor that can bind the type 3 interferons thus negatively regulating signaling.[9]
Clinical significance
Studies show that signaling of the interferon lambdas via the IL-28R reduces tumorigenicity of cancer cells and causes apoptosis.[9]In addition, increasing expression of IL-28R increases the anticancer effects of interferon lambdas.[9] The signaling cascade from the receptor has also been seen to reduce proliferation on human cell lines such as the BON1 pancreatic neuroendocrine tumor cell lines.[9]Signaling through the IL-28R also protects against viruses such as encephalomyocarditis virus and vesicular stomatitis virus as well as the hepatitis B virus in hepatocytes.[1]
References
External links
- Receptors,+Interleukin-28 at the U.S. National Library of Medicine Medical Subject Headings (MeSH)