The interleukin-23 receptor is a
type I cytokine receptor. It is encoded in human by the ''IL23R'' gene.
In complex with the interleukin-12 receptor β1 subunit (
IL-12Rβ1), it is activated by the cytokine
interleukin 23 (IL-23).
The ''IL23R'' mRNA is 2.8 kilobases in length and includes 12 exons. The translated protein contains 629 amino acids; it is a type I penetrating protein and includes a signal peptide, an N-terminal fibronectin III-like domain and an intracellular part that contains three potential tyrosine phosphorylation domains.
There are 24 ''IL23R'' splice variants in mitogen-activated lymphocytes. ''IL23R'' includes some
single-nucleotide polymorphisms in the region encoding the domain that binds IL-23, which may lead to differences between people in Th17 activation. There is also a variant of IL-23R that consists of just the extracellular part and is known as soluble IL-23R. This form can compete with the membrane-bound form to bind IL-23, modulating the Th17 immune response and regulation of inflammation and immune function.
Function
The protein encoded by this gene is a subunit of the receptor for
IL-23. This protein pairs with the receptor molecule IL-12Rβ1 (
IL12RB1 IL-1 may refer to:
* Interleukin 1, a protein
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The Apple Campus is the former corporate headquarters of Apple Inc. from 1993 until 2017, when it wa ...
), together forming the IL-23 receptor complex, and both are required for IL-23 signaling. This protein associates constitutively with Janus kinase 2 (
JAK2) and also binds to transcription activator
STAT3 in a ligand-dependent manner.
Clinical significance
Three variants in the ''IL23R'' gene have been shown to protect against
Crohn's disease
Crohn's disease is a type of inflammatory bowel disease (IBD) that may affect any segment of the gastrointestinal tract. Symptoms often include abdominal pain, diarrhea (which may be bloody if inflammation is severe), fever, abdominal distension ...
and
ulcerative colitis.
The effect of IL-23R variations present in the population have been studied with an in vitro expression model system.
Model organisms
A conditional
knockout mouse line called ''Il23r
tm2a(EUCOMM)Wtsi'' was generated at the
Wellcome Trust Sanger Institute.
Male and female animals underwent a standardized
phenotypic screen to determine the effects of deletion.
In-depth immunological phenotyping was also undertaken.
References
Further reading
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External links
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{{Interleukin receptor modulators
Type I cytokine receptors