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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
General
interleukin
molecular complex
Properties
COMPARTMENT: extracellular compartment
SUBUNITS: interleukin-27 subunit alpha
COMPARTMENT: extracellular compartment
MOTIF: signal sequence {1-28}
glutamate-rich region {164-176}
MOTIF: glutamate residue (SEVERAL)
interleukin-27 subunit beta
MOTIF: signal sequence {1-20}
fibronectin type III domain or F3 module {24-124}
MOTIF: N-glycosylation site {N55}
N-glycosylation site {N105}
fibronectin type III domain or F3 module {129-221}
Database Correlations
OMIM 606746
UniProt Q969H8
References
- UniProt :accession Q969H8
- Wikipedia; Note: interleukin-27 entry
http://en.wikipedia.org/wiki/interleukin_27
Components
interleukin-27 subunit alpha; IL-27 subunit alpha; IL-27-A; IL27-A; p28 (IL27A)
interleukin-27 subunit beta; IL-27 subunit beta; IL-27B; Epstein-Barr virus-induced gene 3 protein; EBV-induced gene 3 protein (EBI3, IL27B)