Interleukin 27

Signal transduction

When IL-27 binds to the IL-27 receptor, signaling pathways including JAK-STAT 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 cells, 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 cells; IL-27 is greatly involved in differentiation through inducing or suppressing of each T cell subset. Th1 cells, which express IFNγ, are generated by IL-27 through STAT1 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. Th17 cells, which express IL-17, IL-22, and granulocyte 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.

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 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

References

1. (April 2015). "The immunobiology of interleukin-27". Annual Review of Immunology.
2. (December 2015). "IL-27-induced modulation of autoimmunity and its therapeutic potential". Autoimmunity Reviews.
3. (September 2015). "Potential clinical application of interleukin-27 as an antitumor agent". Cancer Science.
4. (January 2015). "Interleukin-27 in T cell immunity". International Journal of Molecular Sciences.
5. (October 2015). "The biology of interleukin-27 reveals unique pro- and anti-inflammatory functions in immunity". Cytokine & Growth Factor Reviews.
6. (October 2014). "IL-27 inhibits IFN-γ induced autophagy by concomitant induction of JAK/PI3 K/Akt/mTOR cascade and up-regulation of Mcl-1 in Mycobacterium tuberculosis H37Rv infected macrophages". The International Journal of Biochemistry & Cell Biology.
7. (2012-01-01). "Role of interleukin 10 transcriptional regulation in inflammation and autoimmune disease". Critical Reviews in Immunology.