Advances of the interleukin-21 signaling pathway in immunity and angiogenesis.

Interleukin-21 (IL-21) and its receptor (IL-21R) are broadly expressed on human B cells, activated T cells and other myeloid cells. IL-21 cooperates with IL-6 and transforming growth factor-β to regulate T-cell differentiation. IL-21-mediated human B cell and dendritic cells differentiation requires signal transducer and activator of transcription 3 (STAT3), and also induces B-cell apoptosis dependents on the Toll-like receptor signal. Recently, in vitro and in vivo experiments showed that IL-21/IL-21R regulate angiogenesis through STAT3. IL-21 signaling pathways are complex due to its cooperation with other transcriptional factors, such as interferon regulatory factor 4 and granulocyte-macrophage colony-stimulating factor. The Janus kinase-STAT pathway has been the most extensively studied. With the increase in the understanding of IL-21 biology in the context of each specific disease or pathological condition, IL-21 could be a new therapeutic target for immune-related disease.