The IL-23/IL-17 axis plays an important role in the development of chronic inflammation and in host defenses against bacterial infection. (A) In chronic inflammation, antigen-stimulated dendritic cells and macrophages produce IL-23, which promotes the development of Th17/Th_IL-17 cells. Th17/Th_IL-17 cells produce IL-17, which enhances T cell priming and triggers potent inflammatory responses by inducing the production of a variety of inflammatory mediators. IL-23 also acts on dendritic cells and macrophages in an autocrine/paracrine manner to stimulate the generation of proinflammatory cytokines, such as IL-1, IL-6, and TNF-α. IL-12–stimulated Th1 cells produce IFN-γ and suppress the differentiation of Th17/Th_IL-17 cells. Th1 cells may play an immunoregulatory, not a pathogenic, role in the development of chronic inflammation. (B) Upon bacterial infection, IL-23 is rapidly produced by activated macrophages and dendritic cells at the site of infection. IL-23 then activates local resident Th17/Th_IL-17 cells and other IL-17–producing cells, such as CD8⁺ T cells and γδ T cells. Production of IL-17 by these cells induces G-CSF production from stromal cells. The IL-23/IL-17/G-CSF pathway augments neutrophil recruitment to the infection site, contributing to extracellular bacterial clearance. IL-23 also increases the production of IL-1, IL-6, and TNF-α in an autocrine/paracrine manner. In contrast, Th1 cells produce IFN-γ and stimulate CD8⁺ cytotoxic T lympocytes, NK cells, and macrophages. IFN-γ enhances antigen presentation by inducing expression of MHC molecules and activates cells to produce cytolytic molecules, including perforin and granzyme, which promote the elimination of intracellular bacteria.