Interleukin 27 (IL-27) is a member of the IL-12 cytokine family. It is a heterodimeric

cytokine Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in autocrin ...

that is encoded by two distinct genes, Epstein-Barr virus-induced gene 3 (EBI3) and IL-27p28. IL-27 is expressed by

antigen presenting cells An antigen-presenting cell (APC) or accessory cell is a cell that displays antigen bound by major histocompatibility complex (MHC) proteins on its surface; this process is known as antigen presentation. T cells may recognize these complexes using ...

and interacts with a specific cell-surface receptor complex known as

IL-27 receptor The interleukin-27 receptor is a type I cytokine receptor for interleukin-27. It is a heterodimer composed of the interleukin 27 receptor, alpha subunit and glycoprotein 130. IL27RA essential for transcriptional activation of STAT1 and for a ...

(IL-27R). This receptor consists of two proteins, IL-27ɑ and gp130. IL-27 induces differentiation of the diverse populations of T cells in the immune system and also upregulates IL-10.

Signal transduction

When IL-27 binds to the IL-27 receptor, signaling pathways including

JAK-STAT The JAK-STAT signaling pathway is a chain of interactions between proteins in a cell, and is involved in processes such as immunity, cell division, cell death, and tumour formation. The pathway communicates information from chemical signals out ...

and p38 MAPK pathways are turned on. There are two types of responses, pro-inflammatory and anti-inflammatory, which involve different types of cells, such as macrophages, dendritic cells,

T cell A T cell is a type of lymphocyte. T cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell r ...

s, and B cells. The response that is activated is very much dependent on the external surrounding of IL-27.

Differentiation of T cells

There are many different subsets of T cells, such as Th1, Th2, Th17, Tr1, and

Treg The regulatory T cells (Tregs or Treg cells), formerly known as suppressor T cells, are a subpopulation of T cells that modulate the immune system, maintain tolerance to self-antigens, and prevent autoimmune disease. Treg cells are immunosu ...

cells; IL-27 is greatly involved in differentiation through inducing or suppressing of each T cell subset. Th1 cells, which express

IFNγ Interferon gamma (IFN-γ) is a dimerized soluble cytokine that is the only member of the type II class of interferons. The existence of this interferon, which early in its history was known as immune interferon, was described by E. F. Wheelock ...

, are generated by IL-27 through

STAT1 Signal transducer and activator of transcription 1 (STAT1) is a transcription factor which in humans is encoded by the ''STAT1'' gene. It is a member of the STAT protein family. Function All STAT molecules are phosphorylated by receptor associ ...

dimerization and nuclear localization which subsequently leads to the expression of T-bet and signature Th1 genes. Th2 cells, which express IL-4, are inhibited by IL-27 through the transcription factor

GATA-3 GATA3 is a transcription factor that in humans is encoded by the ''GATA3'' gene. Studies in animal models and humans indicate that it controls the expression of a wide range of biologically and clinically important genes. The GATA3 transcription ...

. Th17 cells, which express IL-17, IL-22, and

granulocyte macrophage colony-stimulating factor Granulocyte-macrophage colony-stimulating factor (GM-CSF), also known as colony-stimulating factor 2 (CSF2), is a monomeric glycoprotein secreted by macrophages, T cells, mast cells, natural killer cells, endothelial cells and fibroblast ...

(GM-CSF), are inhibited by IL-27 through STAT1 and expression of transcription factor RORγt. Tr1 cells, which express IL-10, are induced by IL-27 through the transcription factor c-Maf. Treg cells are inhibited by IL-27 through STAT1 and STAT3.

IL-10 production

IL-10 acts in an anti-inflammatory manner by suppressing inflammatory responses. One way that IL-27 can have an anti-inflammatory response is through the expression of IL-10. IL-27 has been found to be involved in the production of IL-10 by stimulating the various subsets of T cells, especially Tr1 cells. Also involved are the STAT1 and

STAT3 Signal transducer and activator of transcription 3 (STAT3) is a transcription factor which in humans is encoded by the ''STAT3'' gene. It is a member of the STAT protein family. Function STAT3 is a member of the STAT protein family. In respons ...

transcription factors that bind specifically to the receptor subunits, IL-27ɑ and glycoprotein. IL-27 is able to activate STAT3 signaling, which eventually leads to an increase of IL-10 secretion from Treg cells.

References

{{Reflist Interleukins