Targeting interleukin-21 in inflammatory diseases

IL-21, a new member of the type 1 cytokine superfamily, is produced by various subsets of CD4(+) T cells and binds to a composite receptor that consists of a specific receptor, termed IL-21 receptor and the common γ-chain subunit. Initially considered to be a critical regulator of T and B cell function, IL-21 is now known to regulate the activity of many other cell types, including both immune and non-immune cells.

In this review, we discuss the biological features of IL-21 and summarize recent advances in the pathogenic role of IL-21 in chronic inflammatory diseases. Moreover, we discuss why IL-21 blockers can have a place in the therapeutic armamentarium for patients with immune-mediated diseases and the potential risks of such treatments.

Data emerging from studies in human and experimental models of autoimmunity suggest that IL-21 is critically involved in the initiation and/or progression of inflammatory reactions where self-reactive immune cells or antibodies cause damage in tissue. Thus, theoretically, targeting IL-21 could help attenuate the activation of inflammatory pathways and facilitate the resolution of tissue damaging immune responses. However, one should also take into consideration some potential risks that could derive from the blockade of IL-21.