IL-12 Family Cytokines and Their Immune Functions

Cytokines are crucial signaling molecules involved in regulating immune responses. They modulate the behavior of immune cells and contribute to the coordination of diverse physiological processes. In particular, the interleukin-12 (IL-12) family of cytokines has garnered significant attention due to their pivotal roles in immune regulation and disease pathogenesis.

IL-12 Family Cytokines

The IL-12 family consists of IL-12, IL-23, and IL-27, each having distinct structural and functional properties. These cytokines are chiefly produced by antigen-presenting cells and various other immune cell types. Their signaling pathways orchestrate the activation, differentiation, and effector functions of T cells, thereby influencing both innate and adaptive immune responses.

They are the only heterodimeric cytokine family and this endows them with several unique and distinctive features. The heterodimeric IL-12 family cytokines consist of an α chain (p19, p28 or p35) and a β chain (p40 or Ebi3). Alpha chains have a four-helix bundle structure characteristic of the IL-6 superfamily, to which the IL-12 family belongs. In contrast, the β chains share homology with soluble class I cytokine receptor chains, such as IL-6Rα. The p40 chain can pair with p35 or p19 to form IL-12 or IL-23, respectively, while Ebi3 can pair with p28 or p35 to form IL-27 or IL-35, respectively.

Fig. 1 Architecture of the IL-12 cytokine family. (Vignali DA and Kuchroo VK, 2012)

Biological Functions

The biological functions of IL-12 family cytokines encompass a wide array of immunomodulatory activities. IL-12, for instance, plays a critical role in enhancing the cytotoxicity of natural killer cells and initiating T-helper 1 (Th1) cell differentiation. IL-23, on the other hand, is involved in the expansion and maintenance of Th17 cells, contributing to the regulation of autoimmune and inflammatory responses. Furthermore, IL-27 exerts both pro- and anti-inflammatory effects, modulating immune cell functions in diverse physiological contexts.

Immunoregulatory Functions

IL-12 family cytokines exert profound immunoregulatory functions by modulating the activities of various immune cell subsets. They regulate the production of cytokines, such as interferon-gamma (IFN-γ), interleukin-17 (IL-17), and interleukin-10 (IL-10), which are pivotal for shaping immune responses and maintaining immune homeostasis. Additionally, these cytokines influence the recruitment and activation of immune cells at sites of inflammation, thus contributing to the orchestration of effective host defense mechanisms.

• IL-12. Primarily associated with the induction of Th1 responses, IL-12 is vital for host defense against intracellular pathogens and tumors. It promotes the differentiation of CD4+ T cells into IFN-γ-producing effector cells, thereby enhancing cell-mediated immunity.
• IL-23. IL-23 plays a crucial role in supporting the expansion and maintenance of Th17 cells, which are implicated in the pathogenesis of various autoimmune diseases, including rheumatoid arthritis, psoriasis, and inflammatory bowel diseases.
• IL-27. This cytokine exhibits immunoregulatory properties by regulating the balance between pro-inflammatory and anti-inflammatory responses. It can potentially limit excessive inflammation and modulate immune cell activities in diverse pathological conditions.

Therapeutic Applications

Understanding the immunoregulatory functions of IL-12 family cytokines has paved the way for exploring their therapeutic potential. Targeting these cytokines has emerged as a promising strategy for modulating immune responses in the context of infectious diseases, autoimmune disorders, and cancer. By harnessing the immunomodulatory properties of IL-12 family cytokines, researchers and pharmaceutical companies are actively developing novel immunotherapies and vaccines aimed at bolstering immune surveillance and combating immune-related pathologies.

Creative Bioarray Relevant Recommendations

Creative Bioarray offers a large variety of cytokine and growth factors with validated bioactivity, high purity, and low endotoxin. Additionally, we produce our GMP-grade cytokines and growth factors for use as ancillary reagents in ex vivo cell manufacturing.

Reference

1. Vignali DA, Kuchroo VK. (2012). "IL-12 family cytokines: immunological playmakers." Nat Immunol. 13 (8), 722-8.

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