Interleukin- 23 (IL-23), which belongs to the IL-12 family of cytokines, has previously been described as having either redundant functions with IL-12 or promoting the differentiation of a novel CD4 T cell subset that produces IL-17. However, our data is the first to indicate that IL-23 can also negatively regulate the secretion of IFN-gamma that is induced by IL-12. Furthermore, we have also shown that IL-23 is involved in promoting IL-17 secreting CD8T cells. Our results have led us to hypothesize that IL-23 plays a novel and important role in CD8 T cell immunity against pathogens by antagonizing IL-12 induced effector functions and promoting the secretion of IL-17.
In specific Aim I, we will determine which CD8 T cell effector functions are regulated by IL-23 and whether or not IL-23 plays a role in regulating IFN-gamma production in response to infections.
Specific Aim II will identify the mechanisms and signaling pathways involved in IL-23 mediated regulation of IL-12 induced effector functions. Finally, specific Aim III will determine the role of IL- 23 in promoting the secretion of IL-17 from CD8 T cells. The information gathered from these specific aims will increase our knowledge of how IL-23 can regulate early immune responses against pathogens, by decreasing IFN-gamma production and other CD8 T cell effector functions. These studies will also delineate how IL-23 can impact the generation of adaptive immune responses by promoting IL-17 secreting CD8 T cell responses. The results of the experiments outlined within this proposal will further our knowledge of the role of cytokines, particularly IL-23, in immune responses to infectious pathogens. Understanding immune responses to disease causing microbes will enable us to more efficiently control these diseases. ? ? ?
