Interleukin‐12: Central Roles in Immune Regulation and Disease Therapy

ABSTRACT Interleukin‐12 (IL‐12) is a key immunoregulatory cytokine produced primarily by antigen‐presenting cells. During infection, IL‐12 orchestrates innate immune responses and shapes the nature of subsequent adaptive immunity. Specifically, by promoting interferon‐γ (IFN‐γ) production in helper and cytolytic T cells and natural killer (NK) cells, it promotes the activation of these cells and drives the differentiation of CD4 + T cells into type 1 T helper (Th1) cells. IL‐12 is a heterodimeric cytokine composed of the p35 and p40 subunits, whose coordinated expression is required for formation of the bioactive p70 molecule. The promiscuous use of these subunits within the IL‐12 cytokine family, where p40 and p35 also pair with other partners to form IL‐23, IL‐27, and IL‐35, creates structural and functional overlap that enables fine‐tuned immune regulation. Given its potent immune functions, it is not surprising that IL‐12 availability is regulated at multiple levels, including gene transcription, subunit assembly, and shared receptor signaling components. In this review, we provide an overview of IL‐12, how it is produced and secreted and its mechanisms of action. We also discuss the targeting of IL‐12 for the treatment of various diseases, including bacterial infections, autoimmune diseases, and cancer.