IL-27 is a 50 kDa glycoprotein formed by non-covalent bonding of EBI3 (34 kDa) and p28 (28 kDa) . The EBI3 subunit shares structural homology with IL-12p40, while p28 resembles IL-12p35 . Key features include:
IL-27 is predominantly produced early during immune activation by APCs, with macrophages in secondary lymphoid organs identified as major contributors .
IL-27 binding to its receptor activates JAK-STAT and p38 MAPK pathways, with STAT1 and STAT3 being primary mediators :
STAT1 Activation: Drives pro-inflammatory responses, inducing genes like SOCS1, IRF1, and CXCL10 in human monocytes .
STAT3 Activation: Modulates anti-inflammatory effects, including IL-10 upregulation in T cells .
Cross-Regulation: TLR ligands (e.g., LPS) inhibit IL-27 signaling via p38-mediated suppression, limiting its pro-inflammatory effects during later immune phases .
Pro-Inflammatory Effects:
Antiviral Activity: Restricts HIV-1 replication in macrophages by downregulating β2-spectrin and inducing autophagy .
T Cell Differentiation:
Regulatory Functions: Inhibits Treg cell activity and limits dendritic cell antigen presentation under steady-state conditions .
Autoimmunity: IL-27 attenuates pathological Th17 responses in diseases like multiple sclerosis but exacerbates inflammation in rheumatoid arthritis by enhancing myeloid cell activation .
Infections:
Cancer: IL-27 enhances antitumor NK and CD8+ T cell activity but may support immunosuppressive microenvironments via IL-10 .
Antiviral Strategies: Recombinant IL-27 reduces cytopathic effects of viruses like Encephalomyocarditis virus (EMCV) in hepatoma cells .
Recombinant human IL-27 is a glycosylated heterodimer produced in HEK cells. It comprises two polypeptide chains: IL27A (IL27p28) with a molecular weight of 25 kDa and IL27B (EBI3) with a molecular weight of 30 kDa. These chains separate during SDS-PAGE analysis.
The purification of IL-27 protein is achieved through specialized chromatographic methods.
IL-27 plays a crucial role in the regulation of the immune response. It has both pro-inflammatory and anti-inflammatory properties, making it a versatile cytokine in immune modulation. Some of its key functions include:
Recombinant human IL-27 is a synthetic form of the cytokine produced using recombinant DNA technology. It is optimized for use in various research applications, including cell culture, differentiation studies, and functional assays . The recombinant protein is typically produced in HEK293 cells and is available in research-grade quality, with high purity and low endotoxin levels .
Recombinant IL-27 is widely used in scientific research due to its diverse biological activities. Some of the key research areas include: