Il21, or interleukin-21, is a cytokine that plays a crucial role in the immune system. CD4 T cells are the primary producers of Il21, often with the Il21-producing CD4 T cells expressing molecules associated with follicular helper cells (TFH). Il21 is involved in promoting effector functions and memory differentiation of CD8 T cells, and its signaling is associated with various autoimmune diseases [2].

In the expansion of human natural killer (NK) cells, feeder cells expressing membrane-bound (mb) Il21 alone drive superior yield compared to mbIL15, but mbIL15-based feeder cells drive superior functionality by most measures. However, sequential exposure to mbIl21 followed by mbIL15 is advantageous in achieving significant yields of highly functional NK cells [1].

In the context of autoimmune diseases, elevated Il21 is common in patients' tissues and sera, and CD4 T cell-derived Il21:Il21R signaling in CD8 T cells may have implications for several autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, and others [2]. In shoulder arthritis, Il21 inhibits miR-361-5p, promoting MAP3K9 and aggravating the disease progression [3]. In chronic viral infection, Tfh-cell-derived Il21 sustains effector CD8+ T cell responses [4].

In conclusion, Il21 has diverse functions in the immune system, influencing NK cell expansion, T cell-mediated immune responses, and being associated with autoimmune diseases and arthritis. Studies on Il21 help to understand the immune-related biological processes and the mechanisms of associated diseases, potentially providing new strategies for treatment.