Interleukin 30 forms one chain of the heterodimeric cytokine called interleukin 27, thus it is also called IL27-p28. IL-27 is composed of α chain p28 and β chain Epstain-Barr induce gene-3. The p28 subunit, or IL-30, has an important role as a part of IL-27, but it can be secreted as a separate monomer and has its own functions in the absence of EBI3. The discovery of IL-30 as individual cytokine is relatively new and thus its role in the modulation of the immune response is not fully understood.
Function
IL-30 monomer is believed to have some functions similar to IL-27, even though there are more information and research on the IL-27 than IL-30. Both IL-27 and IL-30 alone can regulate inflammation by inhibiting Th17 cells production using STAT1 pathway. Although IL-30 has similar effect as IL-27 on the production of IL-17, it has a lower efficiency than IL-27. If secreted as a monomer, IL-30 was observed to act as a suppressor of the IL-27 signalling pathway. Similar to subunit p40 of IL-12 which competitively bind to IL-12 receptor complex, IL-30 most likely binds to IL-27 receptor receptor and thus prevents the binding of IL-27. Since part of IL-27R is subunit gp130, which is also part of IL-6R, IL-30 can also act as an antagonist for IL-6 and thus suppress the production of Th17 and Th1 cells. Receptor subunit gp130 plays an important role in receptors for multiple cytokines, there is a possibility that IL-30 can affect also other cytokine signalling. IL-30 can also form an alternative heterodimer with the EBI3 homolog cytokine-like factor 1 called p28/CLF. This complex is produced by dendritic cells. p28/CLF binds to IL-6Rα and gp130 subunits of IL-6 receptor. It stimulates NK cells and thus increases production of IFN-γ. It can also induce production of IgG1c, IgG2c and IgM. Artificially, IL-30 can form a heterodimer with p40 β chain of IL-12 creating novel recombinant protein p28/p40 that is biologically active, which suggest the α and β chains of cytokines from IL-12 family may form different heterodimers in nature. This recombinant protein has suppressive effect on Th17 cells that comes from inhibiting the activation of STAT1 and STAT3pathways, which are normally induced through gp130 receptor by IL-6 and IL-27. p28/p40 also inhibits the expansion of Th1 cells. Both of those functions could potentially be beneficial in treatment of some autoimmune diseases. It has been indicated that IL-30 plays a role in the regulation of prostate and breast cancer. It is linked with tumor progression as well as metastasization.
Structure
IL-30 is a protein from the IL-6 cytokine family with molecular weight of 28 kilodaltons. It is a member of the long-chain, 4-helix bundle family of cytokines, making it structurally similar to IL-6. The human gene for IL-30 is located on chromosome 16p11. This gene for this molecule is now officially called IL-27 under HGNC guidelines.
Therapeutic use
IL-30, or a heterodimer p28/p40, could potentially be used as an immunosuppressant for autoimmune and severe systematic inflammatory diseases. IL-30 could also be a potential target for cancer treatment.
