interleukin-27 (IL-27)

Function

• cytokine with pro- & anti-inflammatory properties, that can regulate T helper cell development, suppress T-cell proliferation, stimulate cytotoxic T cell activity, induce isotype switching in B-cells, & that has diverse effects on innate immune cells
• among its target cells are CD4 T helper cells which can differentiate in TH1 & TH2 cells & IL17 producing helper T-cells (TH17)
• drives rapid clonal expansion of naive but not memory CD4 T-cells
• strongly synergizes with IL-12 to trigger interferon- gamma/IFN-gamma production of naive CD4 T-cells, binds to the cytokine receptor WSX-1/TCCR which appears to be required but not sufficient for IL-27-mediated signal transduction
• IL-27 potentiates the early phase of TH1 response & suppresses TH2 & TH17 differentiation
• induces differentiation of TH1 cells via two distinct pathways, p38 MAPK/TBX21- & ICAM1/ITGAL/ERK-dependent pathways
• induces STAT1, STAT3, STAT4 & STAT5 phosphorylation & activates TBX21/T-Bet via STAT1 with resulting IL12RB2 up-regulation, an event crucial to TH1 cell commitment
• suppresses the expression of GATA3, the inhibitor TH1 cells development
• in CD8 T-cells, it activates STATs as well as GZMB
• IL-27 is a potent inhibitor of TH17 cell development & of IL-17 production
• IL-27 subunit p28 alone is also able to inhibit production of IL17 by CD4 & CD8 T-cells
• while IL-27 suppressed the development of proinflammatory Th17 cells via STAT1, it inhibits the development of anti-inflammatory inducible regulatory T-cells, itreg, independently of STAT1
• IL-27 has also an effect on cytokine production, it suppresses proinflammatory cytokine production such as IL2, IL4, IL5 & IL6 & activates suppressors of cytokine signaling such as SOCS1 & SOCS3
• part from suppression of cytokine production, IL-27 also antagonizes the effects of some cytokines such as IL6 through direct effects on T cells
• another important role of IL-27 is its antitumor activity as well as its antiangiogenic activity with activation of production of antiangiogenic chemokines such as IP-10/CXCL10 & MIG/CXCL9
• in vein endothelial cells, it induces IRF1 (interferon regulatory factor 1) & increases expression of MHC class I2 transactivator/CIITA with resulting up-regulation of MHC class II
• IL-27 also demonstrates antiviral activity with inhibitory properties on HIV-1 replication

Structure

• heterodimer of interleukin 27 alpha & interleukin 27 beta

More general terms

• interleukin
• molecular complex

Database

• OMIM: https://mirror.omim.org/entry/606746
• UniProt: http://www.uniprot.org/uniprot/Q969H8.html