IL-12

IL-12

Target · Cytokine

IL-12 Interleukin-12 subunit alpha · natural killer cell stimulatory factor 1

IL-12 is a heterodimeric cytokine whose alpha subunit, encoded by IL12A (also known as p35, CLMF, NKSF1 and NFSK), pairs with IL12B. It regulates T-cell and natural killer-cell responses and links innate resistance to adaptive immunity. Browse Assay Genie's current range of IL-12 research reagents below, or read on for the biology behind the target.

Secreted cytokineDrives Th1 differentiationAlso forms IL-35
219 aa
Protein length
~25 kDa
Molecular weight
3q25.33
Gene locus
IL-6 superfamily
Protein family
Target information

What is IL-12 (interleukin 12A)?

IL-12 is formed when the alpha subunit encoded by IL12A heterodimerises with IL12B. The cytokine is produced mainly by professional antigen-presenting cells such as B-cells and dendritic cells, as well as macrophages and granulocytes. It regulates T-cell and natural killer-cell responses, induces the production of interferon-gamma (IFN-gamma) and favours the differentiation of T-helper 1 (Th1) cells, making it an important link between innate resistance and adaptive immunity.

IL-12 acts through a receptor composed of IL12R1 and IL12R2 subunits. Receptor binding triggers rapid tyrosine phosphorylation of cellular substrates, including the JAK family kinases TYK2 and JAK2. STAT4 is then recruited and phosphorylated, and it translocates to the nucleus to regulate cytokine- and growth factor-responsive genes. NCBI Gene notes that the cytokine is required for T-cell-independent induction of IFN-gamma and contributes to the differentiation of both Th1 and Th2 cells, and that nitric oxide synthase 2 (NOS2) is required for its signalling in innate immunity.

The IL-12 alpha subunit is a secreted protein that belongs to the IL-6 superfamily and sits in the HGNC group of interleukin 12 type subunits. The same subunit also pairs with EBI3 (IL27B) to form IL-35. In that context it helps maintain immune homeostasis in the liver microenvironment and acts as an immune-suppressive cytokine, signalling through unconventional receptors made of IL12RB2 and gp130 (IL6ST) heterodimers or homodimers, with a STAT1–STAT4 heterodimer that binds distinct DNA sites. The gene was previously named natural killer cell stimulatory factor 1 and cytotoxic lymphocyte maturation factor 1, and mouse and rat both carry an Il12a ortholog.

Th1 immune responses

IL-12 favours Th1 cell differentiation and induces IFN-gamma, so it is central to studies of T-helper polarisation.

Innate and adaptive immunity

As a product of antigen-presenting cells that regulates T and NK cells, IL-12 is used to study how innate signals shape adaptive responses.

JAK–STAT4 signalling

IL-12 receptor engagement activates TYK2, JAK2 and STAT4, providing a defined route for studying cytokine-driven gene regulation.

IL-35 and immune regulation

The IL-12 alpha subunit also forms IL-35, an immune-suppressive cytokine linked to liver immune homeostasis.

Background

IL-12 frequently asked questions

What does IL-12 do?

IL-12 regulates T-cell and natural killer-cell responses, induces interferon-gamma production and favours Th1 differentiation. It is produced mainly by antigen-presenting cells and signals through IL12R1 and IL12R2, activating TYK2, JAK2 and STAT4. It is an important link between innate resistance and adaptive immunity.

What are the other names for IL-12 and the IL12A gene?

The IL12A gene encodes the alpha subunit, also called p35, CLMF, IL-12A, NFSK and NKSF1. Earlier names were natural killer cell stimulatory factor 1 and cytotoxic lymphocyte maturation factor 1. The active IL-12 cytokine is a disulfide-linked heterodimer of this subunit and IL12B.

Is the IL-12 alpha subunit found in other cytokines?

Yes. Besides IL-12, the alpha subunit pairs with EBI3 (IL27B) to form IL-35. Unlike IL-12, IL-35 acts as an immune-suppressive cytokine and signals through IL12RB2 and gp130 combinations. Mouse and rat orthologs are both named Il12a; check the datasheet of any product for its validated reactivity.

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Related targets

Other interleukins, IL-12 family cytokines and immune-regulating mediators with products at Assay Genie.

Gene and protein annotations from HGNC, NCBI Gene and UniProt P29459; product specifications from Assay Genie datasheets.

IL-12 Product listing