New directions in the basic and translational biology of interleukin-27

Interleukin (IL)-27 is a member of the IL-6 and IL-12 family composed of the IL-27p28 and Epstein–Barr virus-induced gene 3 (EBI3) subunits. Although IL-27 was originally identified as a proinflammatory factor, subsequent studies have revealed the pleiotropic nature of this cytokine. This review discusses recent work that has explored the effect of IL-27 on CD4+ T cell subsets, including T regulatory type 1 (Tr-1) cells, T follicular helper cells (Tfhs), and forkhead box P3 (Foxp3)+ T regulatory cells (Tregs). Additionally, we highlight studies that have identified a role for the IL-27p28 subunit as a cytokine receptor antagonist. Much of the recent work on IL-27 has been relevant to human disease states characterized by inappropriate or excessive inflammation, and this review discusses potential opportunities to use IL-27 as a therapeutic agent.