IL-21 Signaling and Induction of Cytokine Expression in Human Leukemia Cells and Monocytes

Interleukin-21 (IL-21) is produced by activated T cells and it plays many diverse roles by regulating the functions of normal and abnormal cells. Its roles include regulation of proliferation, promotion of immune system and activation of apoptosis in B cells. IL-21R is a type-1 cytokine receptor and belongs to the IL-2R and IL-15R family. The signaling mechanisms of IL-21 in different cell types have been identified. However, we know less about the biological effects of IL-21 and its signaling mechanisms in leukemia cells and monocytes. In this chapter, we will focus on IL-21’s biological effects and signaling pathways as well as discuss the potential implications and applications of IL-21 in leukemia cells. In these cells, IL-21 does not promote proliferation but enhances apoptosis and chemotaxis. Furthermore, IL-21 promotes differential expression of many cytokines including interleukins and chemokines. IL-21 activates both the Raf-ERK-MAPK and the Jak/STAT signaling pathways. These pathways mediate some of the effects of IL-21. Lastly, IL-21 also promotes activation of the STAT3 promoter and other transcriptional factors. These findings may be relevant to IL-21’s potential clinical implications and applications. in leukemia cells. Our results show that IL-21 activates Jak2, Jak 3 and Tyk2, which are involved in activating several STAT proteins including STAT2, STAT3, STAT4 and STAT6 in both U937 leukemia