IL-27生物学功能的研究进展

Research Progress of Biological Functions of IL-27

白介素-27(interleukin-27,IL-27)是由p28亚基和Epstein-Barr病毒诱导的基因3(Epstein-Barr virus-induced gene 3,EBI3)构成的异源二聚体细胞因子。IL-27具有多重生物学功能,它通过激活下游Janus激酶信号转导/转录激活因子(Janus kinasesignaltransduction/transcriptionalactivator,JAK/STAT)、丝裂原活化蛋白激酶(mitogenactivatedproteinkinases,MAPK)等信号参与调节机体免疫反应、细胞自噬、成骨细胞(osteoblast,OB)和破骨细胞(osteoclast,OC)分化等过程。最新研究证实其在促进脂肪细胞(adipocyte,AD)产热、提高胰岛素敏感性等方面同样具有重要作用。本文就IL-27的结构和生物学功能进行综述,旨在为IL-27的研究和应用提供参考。

Interleukin-27(IL-27) is a heterodimeric cytokine composed of p28 and Epstein-Barr virus-induced 3(EBI3), which belongs to the IL-6/IL-12 family group. IL-27 exerts its biological functions mainly by activating downstream signals such as Janus kinase signal transduction/transcriptional activator(JAK/STAT) and mitogen activated protein kinases(MAPK). Initially, IL-27 was considered to be an inflammatory factor with pro-inflammatory and anti-inflammatory effects. However, with the development of research in recent years, it has been confirmed that IL-27 plays a role in the body’ s immunity and participates in osteogenesis and osteoclast differentiation, phagocytosis and improve insulin sensitivity. IL-27 mainly exerts immunosuppressive effects on CD4+ T cells, CD8+ T cells, and B cells. In CD4+ T cells, IL-27 has dual roles due to different stages of cell differentiation, local microenvironment changes, or activated downstream signals, e. g., IL-27 promotes Th1 cell differentiation in CD4+ T cells and can inhibit differentiation in a highly polarized state of Th1 cells. In CD8+ T cells, IL-27 promotes their proliferative activation and thus plays a role in the immune response and the efficacy of subunit vaccination. In B cells, due to different activation patterns and differentiation stages, IL-27 also has a dual role. It enhances the phosphorylation levels of STAT1 and STAT3 in naive B cells and promotes B cell proliferation;but in memory B cells, its effect is weakened and cannot promote B cell proliferation. In osteoblasts(OB) and osteoclasts(OC), IL-27 promotes OB differentiation mainly through Smad2/3 and STAT1, and inhibits OB differentiation through M-CSF/s RANKL in bone marrow-derived macrophage-like cells OC generation, thereby participating in the regulation of bone growth and remodeling. In addition, the latest research has confirmed that IL-27 can directly target adipocytes, promote adipocyte(AD) thermogenesis, and improve insulin sensitivity through the p38MAPK-PGC-1α signaling pathway, which also suggests that IL-27 plays an important role in metabolic great potential in disease. This article reviews the structure and biological function of IL-27, aiming to provide a reference for the research and application of IL-27.