Il23r, the interleukin-23 receptor, is a crucial component in the interleukin-23 signaling pathway. IL-23 is a cytokine that plays a significant role in regulating the activation and differentiation of lymphocytes. The binding of IL-23 to Il23r initiates signaling cascades, including the STAT3 pathway, which is involved in various biological processes such as immune responses and inflammation [3,5]. Genetic variants in Il23r have been associated with several immune-mediated diseases, highlighting its importance in maintaining immune homeostasis [2,3,4,6,7].

In the context of Crohn's disease, genetic association studies have shown that the IL23R variant rs11209026 is associated with significant protection and follows a recessive mode of inheritance [2]. Engineered Tregs expressing IL23R-CAR (chimeric antigen receptor) for treating active Crohn's disease have been developed. These IL23R-CAR Tregs can migrate to IL23R-expressing tissue in humanized mice, trigger CAR-specific activation, and enhance their suppressive activity, suggesting a promising therapy for active Crohn's disease [1]. In psoriasis, mutations in Il23r lead to differential expression of genes involved in the disease, such as HLA-B, SOCS1, and RUNX3, advancing our understanding of the IL23/psoriasis pathway [3]. Additionally, in alopecia areata, polymorphisms in Il23r are associated with an increased risk of the disease [6].

In conclusion, Il23r is essential for IL-23-mediated signaling in immune responses and inflammation. Studies using genetic association and engineered cell models have revealed its role in diseases like Crohn's disease, psoriasis, and alopecia areata. Understanding Il23r's function provides insights into the pathogenesis of these immune-mediated diseases, potentially leading to the development of novel therapeutic strategies.

References:

1. Cui, Yue, David, Marion, Bouchareychas, Laura, de la Rosa, Maurus, Gertner-Dardenne, Julie. . IL23R-Specific CAR Tregs for the Treatment of Crohn's Disease. In Journal of Crohn's & colitis, 19, . doi:10.1093/ecco-jcc/jjae135. https://pubmed.ncbi.nlm.nih.gov/39252592/

2. 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/

3. 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/

4. Achkar, Jean-Paul. . IL23R and ATG16L1 SNPs in IBD: alphabet soup or something more? In The American journal of gastroenterology, 103, 628-30. doi:10.1111/j.1572-0241.2007.01656.x. https://pubmed.ncbi.nlm.nih.gov/18341487/

5. 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/

6. 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/

7. Naser, Saleh A, Arce, Melissa, Khaja, Anam, Elwasila, Sammer, Thanigachalam, Saisathya. . Role of ATG16L, NOD2 and IL23R in Crohn's disease pathogenesis. In World journal of gastroenterology, 18, 412-24. doi:10.3748/wjg.v18.i5.412. https://pubmed.ncbi.nlm.nih.gov/22346247/