Interleukin-23-receptor

The interleukin-23 receptor is a heteromeric type I cytokine receptor . In humans, it is encoded by the IL23R gene (chromosome 1p31.3).

Together 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 long and comprises 12 exons. The translated protein contains 629 amino acids. It is a type I penetration protein and includes a signal peptide, an N-terminal fibronectin III-like domain, and an intracellular portion containing three potential tyrosine phosphorylation domains.

In mitogen-activated lymphocytes, 24 IL23R splice variants are detectable! Three variants have been shown to protect against Crohn's disease and ulcerative colitis.

One variant of IL-23R has been shown to consist only of the extracellular portion and is known as soluble IL-23R . This form can compete with the membrane-bound form for binding IL-23 and modulates the Th17 immune response and the regulation of inflammation and immune function.

1. Cozzi G et al (2023) Spondyloarthritis with inflammatory bowel disease: the latest on biologic and targeted therapies. Nat Rev Rheumatol 19: 503-518.
2. Duerr RH et al (2006) A genome-wide association study identifies IL23R as an inflammatory bowel disease gene. Science 314:1461-1463
3. Grigoras CA et al (2015) ATG16L1 and IL23R variants and genetic susceptibility to crohn's disease: mode of inheritance based on meta-analysis of genetic association studies. Inflamm Bowel Dis 21:768-776.
4. McGonagle D et al (2021) Why Inhibition of IL-23 Lacked Efficacy in Ankylosing Spondylitis. Front Immunol 12:614255.