IL23R, the interleukin-23 receptor, is a key component in the IL-23 signaling pathway. IL-23 is a cytokine produced by antigen-presenting cells, and IL23R enables cells to respond to this cytokine. The signaling through IL23R involves the STAT3 pathway, which mediates various biological processes such as the activation and differentiation of lymphocytes. Understanding IL23R function is crucial as it is associated with multiple immune-related diseases [3].

Genetic variants in IL23R are linked to several diseases. For instance, the IL23R variant rs11209026 shows a recessive mode of inheritance and is associated with significant protection against Crohn's disease (CD), with a 54% decrease in risk for higher mutational load [1]. In psoriasis, mutations in IL23R lead to differential expression of genes like HLA-B, SOCS1, RUNX3 etc., which are implicated in the IL23 pathway and psoriasis [2]. In alopecia areata, polymorphisms in IL23R (rs10889677) are associated with the risk of developing the disease, specifically the AA genotype with late-onset alopecia areata [4]. Also, expansion of apoptosis-resistant intestinal TNFR2 + IL23R + T cells is associated with resistance to anti-TNF therapy in CD, suggesting IL-23 as a potential molecular target in refractory CD patients [5].

In conclusion, IL23R is essential for IL-23-mediated signaling and lymphocyte regulation. Genetic studies on IL23R have revealed its significance in diseases such as Crohn's disease, psoriasis, and alopecia areata. Understanding the role of IL23R through genetic models provides insights into disease pathogenesis and potential therapeutic targets for these immune-related disorders.

References:

1. Grigoras, Christos A, Ziakas, Panayiotis D, Jayamani, Elamparithi, Mylonakis, Eleftherios. . ATG16L1 and IL23R variants and genetic susceptibility to crohn's disease: mode of inheritance based on meta-analysis of genetic association studies. In Inflammatory bowel diseases, 21, 768-76. doi:10.1097/MIB.0000000000000305. https://pubmed.ncbi.nlm.nih.gov/25738374/

2. Rane, Shraddha S, Shellard, Elan, Adamson, Antony, Eyre, Steve, Warren, Richard B. . IL23R mutations associated with decreased risk of psoriasis lead to the differential expression of genes implicated in the disease. In Experimental dermatology, 33, e15180. doi:10.1111/exd.15180. https://pubmed.ncbi.nlm.nih.gov/39306854/

3. Glassman, Caleb R, Mathiharan, Yamuna Kalyani, Jude, Kevin M, Skiniotis, Georgios, Garcia, K Christopher. . Structural basis for IL-12 and IL-23 receptor sharing reveals a gateway for shaping actions on T versus NK cells. In Cell, 184, 983-999.e24. doi:10.1016/j.cell.2021.01.018. https://pubmed.ncbi.nlm.nih.gov/33606986/

4. Tabatabaei-Panah, Pardis-Sadat, Moravvej, Hamideh, Delpasand, Sara, Ludwig, Ralf J, Akbarzadeh, Reza. 2020. IL12B and IL23R polymorphisms are associated with alopecia areata. In Genes and immunity, 21, 203-210. doi:10.1038/s41435-020-0100-1. https://pubmed.ncbi.nlm.nih.gov/32355229/

5. Schmitt, Heike, Billmeier, Ulrike, Dieterich, Walburga, Neurath, Markus F, Atreya, Raja. 2018. Expansion of IL-23 receptor bearing TNFR2+ T cells is associated with molecular resistance to anti-TNF therapy in Crohn's disease. In Gut, 68, 814-828. doi:10.1136/gutjnl-2017-315671. https://pubmed.ncbi.nlm.nih.gov/29848778/