Regulation of Defense Responses against Protozoan Infection by Interleukin-27 and Related Cytokines

Cytokine-mediated immunity is crucial in the defense against pathogens. Recently, IL-23 and IL-27 were identified, which along with IL-12 belong to the IL-12 cytokine family. IL-27 is pivotal for the induction of helper T cell (Th) 1 responses while IL-23 is important for the proliferation of memory type Th1 cells. Recent studies revealed that IL-27 also has an anti-inflammatory property. In some protozoan infection, various proinflammatory cytokines were over produced causing lethal inflammatory responses in IL-27 receptor-deficient mice. The anti-inflammatory effect of IL-27 depends, at least partly, on inhibition of the development of Th17 cells, a newly identified Th population that is induced by IL-23 and is characterized by the production of the inflammatogenic cytokine, IL-17. IL-27 thus has a double identity as an initiator and as an attenuator of immune responses and inflammation. With the discoveries of the new IL-12-related cytokines and Th17 cells, Th development is facing a new paradigm.