IL21, interleukin-21, is a cytokine that plays a crucial role in the immune system. It is mainly produced by CD4 T cells, often those associated with follicular helper cells (TFH). IL21 is involved in promoting effector functions and memory differentiation of CD8 T cells in chronic infections and cancer, and also has implications in autoimmune diseases [2].

In natural killer (NK) cell expansion, using feeder cells expressing membrane-bound (mb) IL21 alone drives superior yield, while mbIL15-based feeder cells drive superior functionality. Sequential exposure to mbIL21 followed by mbIL15 can achieve significant yields of highly functional NK cells, highlighting the plasticity of NK cell differentiation [1]. In autoimmune diseases, elevated IL21 is a common finding. For example, in systemic lupus erythematosus, the lncRNA IL21-AS1 can promote IL21 overexpression and aberrant differentiation of Tfh cells, which is important in the pathogenesis of the disease [3,4].

In conclusion, IL21 is essential for immune-related functions such as NK cell expansion, T cell differentiation, and is closely associated with autoimmune diseases. Studies using various models, including those related to IL21-AS1 in the context of SLE, help to reveal its role in these biological processes and disease conditions, providing insights for potential therapeutic strategies.

References:

1. Zhang, Caimei, Kadu, Siddhant, Xiao, Yansen, June, Carl H, Sheppard, Neil C. . Sequential Exposure to IL21 and IL15 During Human Natural Killer Cell Expansion Optimizes Yield and Function. In Cancer immunology research, 11, 1524-1537. doi:10.1158/2326-6066.CIR-23-0151. https://pubmed.ncbi.nlm.nih.gov/37649085/

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. Hao, He, Nakayamada, Shingo, Ohkubo, Naoaki, Zhang, Tong, Tanaka, Yoshiya. 2021. Involvement of lncRNA IL21-AS1 in interleukin-2 and T follicular regulatory cell activation in systemic lupus erythematosus. In Arthritis research & therapy, 23, 302. doi:10.1186/s13075-021-02682-w. https://pubmed.ncbi.nlm.nih.gov/34895341/

4. Liu, Limin, Hu, Longyuan, Long, Haojun, Lu, Qianjin, Zhao, Ming. . LncRNA IL21-AS1 interacts with hnRNPU protein to promote IL21 overexpression and aberrant differentiation of Tfh cells in systemic lupus erythematosus. In Clinical and translational medicine, 12, e1117. doi:10.1002/ctm2.1117. https://pubmed.ncbi.nlm.nih.gov/36447054/