Biological effects of IL-21 on different immune cells and its role in autoimmune diseases

Interleukin-21 (IL-21) is a member of the common γ-chain cytokines with broad pleiotropic actions that affects different immune and nonimmune cells. IL-21 can affect differentiation, proliferation and function of T and B cells; it can also induce the maturation and enhance the cytotoxicity of CD8+ T cells and Natural killer (NK) cells. IL-21 exerts major effects on B-cell activation and differentiation or apoptosis during humoral immune responses and induces differentiation of naïve B cells and memory B cells into plasma cells. IL-21 also affects different subtypes of T cells including T helper-17 (TH17), T follicular helper (TFH) and regulatory T (Treg) cells and thereby promotes the development of autoimmune disorders and inflammatory diseases. Observations have shown that the blockade of IL-21 has therapeutic effects on various autoimmune diseases in animal models. A better understanding of the regulation of cell differentiation and stabilization by IL-21 in the context of each specific autoimmune disease or tissue-specific pathological microenvironments will be helpful in developing novel treatments to control autoimmune diseases. Herein, we review the biological effects of IL-21 on different immune cells and uncover the emerging role of this interesting cytokine in autoimmune diseases.