IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. This study shows that IL-23 is essential for the expansion of a pathogenic CD4+ T cell population that produces IL-17, IL-17F, IL-6, and TNF, which are critical for organ-specific autoimmune inflammation. Unlike IL-12, which promotes IFN-γ-producing Th1 cells, IL-23 supports the development of IL-17-producing Th17 cells. These Th17 cells are highly pathogenic and essential for the establishment of autoimmune inflammation, particularly in models of experimental autoimmune encephalomyelitis (EAE) and collagen-induced arthritis (CIA). IL-23-deficient mice are resistant to EAE and CIA, indicating the importance of IL-23 in autoimmune disease pathogenesis. IL-23 promotes the differentiation and expansion of Th17 cells, which are characterized by the production of IL-17, IL-17F, TNF, and IL-6. These cells are distinct from Th1 cells, which are primarily IFN-γ producers. Gene expression analysis reveals that IL-23-driven T cells have a unique cytokine profile, distinguishing them from IL-12-driven T cells. IL-23 is not required for Th1 development but is essential for Th17 cell development. IL-23 also plays a role in the expansion of self-reactive T cells that contribute to autoimmune inflammation. The study highlights the distinct roles of IL-23 and IL-12 in autoimmune disease, with IL-23 being critical for Th17 cell development and function. The findings suggest that targeting IL-23 or its downstream pathways could be a potential therapeutic strategy for inflammatory autoimmune diseases.IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. This study shows that IL-23 is essential for the expansion of a pathogenic CD4+ T cell population that produces IL-17, IL-17F, IL-6, and TNF, which are critical for organ-specific autoimmune inflammation. Unlike IL-12, which promotes IFN-γ-producing Th1 cells, IL-23 supports the development of IL-17-producing Th17 cells. These Th17 cells are highly pathogenic and essential for the establishment of autoimmune inflammation, particularly in models of experimental autoimmune encephalomyelitis (EAE) and collagen-induced arthritis (CIA). IL-23-deficient mice are resistant to EAE and CIA, indicating the importance of IL-23 in autoimmune disease pathogenesis. IL-23 promotes the differentiation and expansion of Th17 cells, which are characterized by the production of IL-17, IL-17F, TNF, and IL-6. These cells are distinct from Th1 cells, which are primarily IFN-γ producers. Gene expression analysis reveals that IL-23-driven T cells have a unique cytokine profile, distinguishing them from IL-12-driven T cells. IL-23 is not required for Th1 development but is essential for Th17 cell development. IL-23 also plays a role in the expansion of self-reactive T cells that contribute to autoimmune inflammation. The study highlights the distinct roles of IL-23 and IL-12 in autoimmune disease, with IL-23 being critical for Th17 cell development and function. The findings suggest that targeting IL-23 or its downstream pathways could be a potential therapeutic strategy for inflammatory autoimmune diseases.