Il21r, the interleukin-21 receptor gene, is a crucial component in the immune system. It is part of the common γ chain cytokine receptor family, which is involved in signaling pathways for cytokines such as IL-21. Signaling through Il21r is important for various immune-related processes, including T-cell and B-cell activation, differentiation, and effector functions, as well as in the regulation of innate immune cells [2,4].

In breast cancer, Il21r hypomethylation has been identified as a biomarker. BC patients showed significant Il21r hypomethylation compared to those with benign breast tumors, and this hypomethylation was more pronounced in ER-negative, PR-negative, and triple-negative tumors. The methylation of Il21r demonstrated efficient discriminatory power in distinguishing benign from malignant breast tumors [1]. In multiple myeloma, CD14+ cells from patients over-expressed Il21r, which was independent of interleukin-21 presence. This over-expression led to increased osteoclast formation, suggesting a role for Il21r in myeloma-enhanced osteoclastogenesis [3]. In metabolic dysfunction-associated steatohepatitis-driven hepatocellular carcinoma, IL-21R signaling promotes the disease by inducing immunosuppressive IgA+ B cells. High IL-21R expression in HCC patients was associated with poor relapse-free survival, advanced TNM stage, and severe steatosis [5].

In conclusion, Il21r plays significant roles in immune-related functions and is implicated in several disease conditions. Research on Il21r, especially through gene-based models, has provided insights into its role in breast cancer, multiple myeloma, and hepatocellular carcinoma, highlighting its potential as a biomarker and therapeutic target in these diseases.

References:

1. Zang, Zishan, Yin, Yifei, Liu, Chunlan, Li, Hong, Yang, Rongxi. 2024. IL21R hypomethylation as a biomarker for distinguishing benign and malignant breast tumours. In Epigenetics, 19, 2352683. doi:10.1080/15592294.2024.2352683. https://pubmed.ncbi.nlm.nih.gov/38723244/

2. Ren, Heather M, Lukacher, Aron E, Rahman, Ziaur S M, Olsen, Nancy J. 2021. New developments implicating IL-21 in autoimmune disease. In Journal of autoimmunity, 122, 102689. doi:10.1016/j.jaut.2021.102689. https://pubmed.ncbi.nlm.nih.gov/34224936/

3. Bolzoni, Marina, Ronchetti, Domenica, Storti, Paola, Aversa, Franco, Giuliani, Nicola. 2017. IL21R expressing CD14+CD16+ monocytes expand in multiple myeloma patients leading to increased osteoclasts. In Haematologica, 102, 773-784. doi:10.3324/haematol.2016.153841. https://pubmed.ncbi.nlm.nih.gov/28057743/

4. Luo, Wei, Conter, Laura, Elsner, Rebecca A, Chikina, Maria, Shlomchik, Mark. 2023. IL-21R signal reprogramming cooperates with CD40 and BCR signals to select and differentiate germinal center B cells. In Science immunology, 8, eadd1823. doi:10.1126/sciimmunol.add1823. https://pubmed.ncbi.nlm.nih.gov/36800413/

5. Xie, Ying, Huang, Yu, Li, Zhi-Yong, Yin, Zhinan, Lin, Xue-Jia. 2024. Interleukin-21 receptor signaling promotes metabolic dysfunction-associated steatohepatitis-driven hepatocellular carcinoma by inducing immunosuppressive IgA+ B cells. In Molecular cancer, 23, 95. doi:10.1186/s12943-024-02001-2. https://pubmed.ncbi.nlm.nih.gov/38720319/