Interleukin 27 (IL-27) is a member of theIL-12 cytokine family. It is a heterodimericcytokine that is encoded by two distinct genes,Epstein-Barr virus-induced gene 3 (EBI3) and IL-27p28. IL-27 is expressed byantigen presenting cells and interacts with a specific cell-surface receptor complex known asIL-27 receptor (IL-27R).[1][2][3][4][5] This receptor consists of two proteins, IL-27Rɑ and gp130. IL-27 induces differentiation of the diverse populations of T cells in the immune system and also upregulatesIL-10.
When IL-27 binds to the IL-27 receptor, signaling pathways includingJAK-STAT and p38 MAPK pathways are turned on.[6][2] There are two types of responses, pro-inflammatory and anti-inflammatory, which involve different types of cells, such asmacrophages,dendritic cells,T cells, andB cells.[3] The response that is activated is very much dependent on the external surrounding of IL-27.[1][2][3]
There are many different subsets of T cells, such as Th1, Th2, Th17,Tr1, andTreg cells; IL-27 is greatly involved in differentiation through inducing or suppressing of each T cell subset.[1][2][4][5] Th1 cells, which expressIFNγ, are generated by IL-27 throughSTAT1 dimerization and nuclear localization which subsequently leads to the expression of T-bet and signature Th1 genes. Th2 cells, which expressIL-4, are inhibited by IL-27 through the transcription factorGATA-3. Th17 cells, which express IL-17, IL-22, andgranulocyte macrophage colony-stimulating factor (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.[2][4][5]
IL-10 acts in an anti-inflammatory manner by suppressing inflammatory responses.[7] 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 andSTAT3 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.[1]