IL12 family

An overview of the IL-12 cytokine family and its role in the immune system

The IL-12 family of cytokines is a group of heterodimeric cytokines that play crucial roles in the regulation of the immune system. These cytokines are involved in the differentiation and activation of T cells, natural killer cells, and other immune cells, influencing both innate and adaptive immune responses.

Structure and Members

The IL-12 family consists of several cytokines, each composed of two subunits. These subunits are shared among different family members, allowing for diverse functional roles. The primary members of the IL-12 family include:

• IL-12: Composed of the p35 and p40 subunits, IL-12 is a key cytokine in promoting Th1 cell differentiation and enhancing the cytotoxic activity of natural killer cells.
• IL-23: Consists of the p19 and p40 subunits. IL-23 is involved in the maintenance and expansion of Th17 cells, which are important in the defense against extracellular pathogens and in the pathogenesis of autoimmune diseases.
• IL-27: Made up of the p28 and EBI3 subunits, IL-27 has both pro-inflammatory and anti-inflammatory roles, influencing the differentiation of T helper cells and the production of interferon gamma.
• IL-35: Composed of the p35 and EBI3 subunits, IL-35 is an anti-inflammatory cytokine that is involved in the regulation of regulatory T cells and the suppression of immune responses.

Biological Functions

The IL-12 family cytokines are critical in shaping the immune response. They are primarily produced by antigen-presenting cells such as dendritic cells and macrophages in response to microbial stimuli.

• IL-12: Promotes the differentiation of naive CD4+ T cells into Th1 cells, which are essential for cell-mediated immunity against intracellular pathogens. IL-12 also enhances the cytotoxic functions of CD8+ T cells and natural killer cells.
• IL-23: Supports the expansion and maintenance of Th17 cells, which produce IL-17 and are involved in the defense against fungi and bacteria, as well as in the development of inflammatory and autoimmune conditions.
• IL-27: Has a dual role, promoting Th1 cell differentiation while also exerting regulatory effects that limit excessive inflammation. IL-27 can inhibit Th17 cell differentiation and promote the development of regulatory T cells.
• IL-35: Functions as an immunosuppressive cytokine, promoting the expansion of regulatory T cells and inhibiting the proliferation of effector T cells, thus maintaining immune homeostasis and preventing autoimmunity.

Clinical Implications

The IL-12 family cytokines are implicated in various diseases, including infectious diseases, autoimmune disorders, and cancers. Therapeutic modulation of these cytokines is being explored for the treatment of conditions such as multiple sclerosis, rheumatoid arthritis, and inflammatory bowel disease.

• Autoimmune Diseases: Dysregulation of IL-23 and IL-17 pathways is associated with autoimmune diseases like psoriasis and ankylosing spondylitis. Targeting these pathways with biologics such as ustekinumab and secukinumab has shown clinical efficacy.
• Cancer: IL-12 has been investigated as an anti-cancer agent due to its ability to enhance anti-tumor immunity. However, its clinical use is limited by toxicity concerns.

Also see

• Cytokine
• Immune system
• T helper cell
• Autoimmune disease
• Interleukin