Interferon Lambda's New Role as Regulator of Neutrophil Function

Neutrophils are increasingly appreciated as multifaceted regulators of innate immunity and inflammation. Historically, these important innate cells have been considered suicidal phagocytes with a primary role in the destruction of extracellular pathogens. Recent studies have significantly altered this simplistic view of neutrophils and have instead presented extensive evidence for a complex role for neutrophils in the control of diverse inflammatory conditions. It is now appreciated that neutrophils are crucial not only for efficient clearance of various pathogens but also in the development and control of inflammatory states such as autoimmunity, cancer, and tissue repair. Mounting evidence also suggests that neutrophils are capable of differential activation giving rise to distinctly polarized cells with diverse effector functions. Interferon lambda (IFN-λ) (also known as type III IFN) has emerged as an unexpected regulator of neutrophil function. IFN-λs are the newest members of the IFN family of antiviral cytokines and although initial studies suggested identical biological activities to type I IFNs, it is now apparent that type III IFN has distinct functions in vivo. In this article, I summarize recent evidence linking type III IFNs to the regulation and potential tailoring of neutrophil responses. These exciting observations might have important implications for the development of IFN-λs as novel therapeutic cytokines for the treatment of a diversity of inflammatory states where neutrophils are crucial players.