IL27
Description
The IL27 (interleukin 27) is a protein-coding gene located on chromosome 16.
Interleukin 27 (IL-27) is a member of the IL-12 cytokine family. It is a heterodimeric cytokine that is encoded by two distinct genes, Epstein-Barr virus-induced gene 3 (EBI3) and IL-27p28. IL-27 is expressed by antigen presenting cells and interacts with a specific cell-surface receptor complex known as IL-27 receptor (IL-27R). This receptor consists of two proteins, IL-27Rɑ and gp130. IL-27 induces differentiation of the diverse populations of T cells in the immune system and also upregulates IL-10.
== 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.
IL-27 is a heterodimeric cytokine formed by IL-27 subunit alpha (IL-27-A) and EBI3. It plays a crucial role in innate immunity, exhibiting both pro- and anti-inflammatory properties. It regulates T-helper cell development, suppressing T-cell proliferation while stimulating cytotoxic T-cell activity. Additionally, it induces isotype switching in B-cells and exerts diverse effects on innate immune cells. IL-27 targets CD4 T-helper cells, promoting their differentiation into type 1 effector cells (TH1), type 2 effector cells (TH2), and IL17 producing helper T-cells (TH17). It drives rapid clonal expansion of naive CD4 T-cells but not memory cells. Synergizing with IL-12, it triggers interferon-gamma/IFN-gamma production in naive CD4 T-cells. IL-27 binds to the cytokine receptor WSX-1/TCCR, which is essential for IL-27-mediated signal transduction. It potentiates the early phase of TH1 response while suppressing TH2 and TH17 differentiation. IL-27 induces TH1 cell differentiation through two pathways: p38 MAPK/TBX21- and ICAM1/ITGAL/ERK-dependent pathways. It also activates TBX21/T-Bet via STAT1 with IL12RB2 upregulation, crucial for TH1 cell commitment. IL-27 inhibits the expression of GATA3, a factor that hinders TH1 cell development. In CD8 T-cells, IL-27 activates STATs and GZMB. It effectively inhibits TH17 cell development and IL-17 production, even independently suppressing IL17 production by CD4 and CD8 T-cells. While IL-27 suppresses pro-inflammatory Th17 cells via STAT1, it inhibits the development of anti-inflammatory inducible regulatory T-cells (iTreg) independent of STAT1. IL-27 also modulates cytokine production, suppressing pro-inflammatory cytokines like IL2, IL4, IL5, and IL6 while activating suppressors of cytokine signaling like SOCS1 and SOCS3. IL-27 antagonizes the effects of certain cytokines, such as IL6, through direct effects on T-cells. IL-27 exhibits antitumor and antiangiogenic activity, stimulating the production of antiangiogenic chemokines like IP-10/CXCL10 and MIG/CXCL9. In vein endothelial cells, IL-27 induces IRF1/interferon regulatory factor 1 and increases MHC class II transactivator/CIITA expression, leading to upregulation of major histocompatibility complex class II. IL-27 also possesses antiviral activity, inhibiting HIV-1 replication. It forms a heterodimer with EBI3, known as interleukin IL-27, but they are not disulfide-linked.
IL27 is also known as IL-27, IL-27A, IL27A, IL27p28, IL30, p28.
