Interleukin-27

Interleukins (from Latin inter = between and Greek λευκός = white and κινεῖν = to move) are a group of endogenous, short-chain regulatory proteins (cytokines) of the immune system (IL1-IL38). Interleukins are mediators for the induction, progression and control of T-cell-mediated cytotoxic immune reactions and B-cell activation (antibody production). They are mainly produced and secreted by stimulated leukocytes, monocytes and macrophages. To date, around 38 different interleukins have been clearly identified. Each cytokine of the interleukin group is assigned a nomenclatural number for its classification (IL-1 to IL-38).

Some structurally related substances have been grouped into families. Their members often have a similar function or are involved in the fine regulation of immune reactions, for example by regulating the synthesis of related interleukins.

Interleukin-27 is a heterodimeric, regulatory cytokine and belongs to the interleukin-12/interleukin-23 family. The cytokine was discovered in 2002.

There is a close molecular relationship between interleukin-27 and interleukin-30. Interleukin-30 forms the alpha subunit of IL-27 (IL-27p28), which is encoded by the Epstein-Barr virus-induced gene 3, also known as EBI3. Despite its identity with the alpha subunit, IL-30 can be formed and secreted independently of IL-27.

It is involved in the pathogenesis of numerous inflammatory (also autoimmunological) diseases. These include rheumatoid arthritis, psoriasis, multiple sclerosis, Crohn's disease, ulcerative colitis and infectious diseases.

IL-27 is expressed by activated macrophages, dendritic cells, CD4+ T-cells (proven in malaria infection) and B cells. The cytokine interacts with its specific surface receptor complex, the IL-27 receptor IL-27R. This receptor complex consists of 2 proteins, IL-27alpha and gp130. After binding to its receptor, the complex activates the JAK/STAT and the p38 MAPK signalling pathway. The immunological effect can be described as dual, since both pro-inflammatory and anti-inflammatory processes are activated. Different cell types such as macrophages, dendritic cells, T and B cells are activated. The development of Th-17 cells is inhibited.

1. Kimura D et al (2016) Interleukin-27-Producing CD4(+) T Cells Regulate Protective Immunity during Malaria Parasite Infection. Immunity 44:672-682.
2. Jung JY et al. (2015) The presence of interleukin-27 during monocyte-derived dendritic cell differentiation promotes improved antigen processing and stimulation of T cells. Immunology 144:649-660.
3. Gao P et al (2016) Transcription factor Fli-1 positively regulates lipopolysaccharide-induced interleukin-27 production in macrophages. Mol immunol 71:184-191.
4. Duan Y et al (2015) Potent therapeutic target of inflammation, virus and tumor: focus on interleukin-27. Int Immunopharmacol 26:139-146.
5. Wong HR et al (2014) Performance of interleukin-27 as a sepsis diagnostic biomarker in critically ill adults. J Crit Care 29:718-722.
6. Yoshida H et al (2015) The immunobiology of interleukin-27 Annu Rev Immunol 33:417-443 .
7. Iwasaki Y et al. (2015) Interleukin-27 in T cell immunity. Int J Mol Sci 16:2851-2863.