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.