IL27

Official Full Name

interleukin 27

Organism

Homo sapiens

GeneID

246778

Background

The protein encoded by this gene is one of the subunits of a heterodimeric cytokine complex. This protein is related to interleukin 12A (IL12A). It interacts with Epstein-Barr virus induced gene 3 (EBI3), a protein similar to interleukin 12B (IL12B), and forms a complex that has been shown to drive rapid expansion of naive but not memory CD4(+) T cells. The complex is also found to synergize strongly with interleukin 12 to trigger interferon gamma (IFNG) production of naive CD4(+) T cells. The biological effects of this cytokine are mediated by the class I cytokine receptor (WSX1/TCRR). [provided by RefSeq, Jul 2008]

Synonyms

p28; IL30; IL-27; IL27A; IL-27A; IL27p28;

Cat.No.	Product Name	Price

Cat.No.	Product Name	Price

Cat.No.	Product Name	Price

Cat.No.	Product Name	Price

Detailed Information

The IL-27 gene encodes a key subunit of the heterodimeric cytokine IL-27, which shares structural homology with interleukin-12A (IL-12A). IL-27 functions as a heterodimer composed of two subunits linked by a disulfide bond: p28 (IL-27A), encoded by IL-27, and EBI3, encoded by the Epstein-Barr virus-induced gene 3. This unique heterodimeric structure positions IL-27 distinctly within the cytokine family, structurally homologous to IL-12 and IL-23, yet functionally unique. IL-27 signaling is mediated through a type I cytokine receptor complex composed of WSX-1 (specific IL-27-binding subunit) and gp130 (a shared signaling subunit used by multiple cytokines), a configuration that enables complex cross-talk with other cytokine pathways.

Biological Significance

IL-27 is a bifunctional immunoregulatory cytokine that can exert both pro-inflammatory effects to assist host defense and anti-inflammatory effects to maintain immune homeostasis and prevent excessive tissue damage. During the initiation of adaptive immunity, IL-27 collaborates with IL-12 to strongly induce IFN-γ production by naïve CD4+ T cells, promoting Th1 differentiation. This involves activation of intracellular signaling networks, including STAT1, STAT3, STAT4, and STAT5 phosphorylation, and upregulation of T-bet and IL-12 receptor β2, reinforcing Th1 lineage commitment.

Figure 1. A schematic model of IL-27 effect on superoxide generation. (Sowrirajan B, et al. 2017)

Conversely, IL-27 suppresses differentiation of Th17 cells and IL-17 production via STAT1-dependent mechanisms, providing protective effects in autoimmune conditions such as experimental autoimmune encephalomyelitis. IL-27 also inhibits Th2 differentiation and regulates induced regulatory T cell development through STAT1-independent pathways. Beyond CD4+ T cells, IL-27 enhances CD8+ T cell cytotoxicity, promotes B cell class-switch recombination, and modulates innate immune cell functions, including monocytes, macrophages, and dendritic cells. Additionally, IL-27 exhibits anti-tumor and anti-angiogenic activity, partly by inducing chemokines such as IP-10 and MIG, and demonstrates potential antiviral effects by inhibiting viral replication.

Clinical Significance

IL-27's dual immunomodulatory properties make it a promising target for therapeutic intervention in infectious diseases, autoimmune disorders, and cancer. In infections, its pro-inflammatory and Th1-promoting activity is critical for defense against intracellular pathogens, while defects may lead to persistent infections. Conversely, pathogens may exploit IL-27's anti-inflammatory effects to evade immunity.

In autoimmune diseases, IL-27's suppression of Th17 responses positions it as a potential therapeutic cytokine; exogenous IL-27 or enhanced signaling has shown efficacy in multiple animal models of autoimmunity. In cancer, IL-27's anti-angiogenic effects and ability to activate CD8+ T cells and NK cells support its role as an anti-tumor cytokine. However, therapeutic modulation is challenging due to the delicate balance between its pro- and anti-inflammatory functions: IL-27 agonists may inadvertently suppress beneficial Th17 or Treg responses, whereas antagonists could reduce essential anti-tumor or anti-infection immunity. Future research aims to elucidate IL-27's tissue- and disease-specific roles and optimize strategies for precise delivery, timing, or combination therapy to safely harness this multifunctional cytokine.

References

Pflanz S, Timans JC, Cheung J, et al. IL-27, a heterodimeric cytokine composed of EBI3 and p28 protein, induces proliferation of naive CD4+ T cells. Immunity. 2002;16(6):779–790.
Andres-Martin F, James C, Catalfamo M. IL-27 expression regulation and its effects on adaptive immunity against viruses. Front Immunol. 2024 Jun 20;15:1395921.
Sowrirajan B, Saito Y, Poudyal D, et al. Interleukin-27 Enhances the Potential of Reactive Oxygen Species Generation from Monocyte-derived Macrophages and Dendritic cells by Induction of p47^phox. Sci Rep. 2017 Feb 27;7:43441.

Quick Inquiry

Interested in learning more?

Contact us today for a free consultation with the scientific team and discover how Creative Biogene can be a valuable resource and partner for your organization.

Request a quote today!

Inquiry