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The family of IL‐12 cytokines – IL‐12, IL‐23, IL‐27 and IL‐35 – are secreted by activated innate DCs and macrophages [1]. Each cytokine can perpetuate autoimmune inflammatory diseases by regulating CD4 T‐cell subsets in the adaptive immune response (Figure 2.2). IL‐12 and IL‐23 are among the most potent proinflammatory cytokines, while IL‐27 and IL‐35 are anti‐inflammatory and immunosuppressive. IL‐12 drives initial and subsequent differentiation of naive CD4 Th0 cells into Th17 cells and γδ T cells to produce inflammatory IL‐17. Recent studies indicate that IL‐21, secreted by Thf and Th9 cells, is the most dominant factor in the generation and maintenance of immunopathology (Figure 2.2).