Interleukin-39 (IL-39) is a recently discovered new member of the IL-12 family, consisting of two subunits of IL-23p19 and EB virus-induced gene 3. It is mainly produced by lipopolysaccharide-stimulated B cells and activated GL7 + B cells in lupus mice. IL-23R / gp130 is its receptor, which is activated by signal transduction and transcriptional activation factor 1 (STAT1)/STAT3 signaling pathway mediates inflammation. The current research on IL-39 is still in its infancy. IL-39 may be an important proinflammatory factor, mainly produced by activated B cells in vivo and in vivo, and can be used as a potential therapeutic target for systemic lupus erythematosus.
Cytokines of the interleukin-12 (IL-12) family are heterodimeric glycoproteins composed of alpha and beta polypeptide chains covalently linked by disulfide bonds. The alpha chain includes IL-23p19 , IL27p28 and IL-12p35, and β chain includes IL-12p40 and Epstein-Barr virus-induced gene 3 (EBI3). Six different heterodimers can be formed by combining any one subunit in α chain and β chain. IL-23p19 and EBI3 subunits can combine to form a new heterodimeric protein, and was officially named IL-39. The two subunits of IL-39, IL-23p19 and EBI3, are shared with IL-23 and IL-27 / IL-35, respectively. The IL-23p19 subunit has a 4α helix bundle structure, which has homology with IL-6 and granulocyte colony stimulating factor. The EBI3 subunit was originally found in EB virus-infected B lymphocytes. Its gene is located on human chromosome 17 and encodes a glycoprotein with a relative molecular mass of 34,000, of which 27% have the same amino acid sequence as the IL-12p40 subunit source.
IL-12 family cytokine receptors are composed of homo- or heterodimers formed by IL-12Rβ1, IL-12Rβ2, IL23R, gp130 and IL-27R. Since the subunits of IL-39 are shared with IL-23, IL-27 and IL-35, respectively, it can be reasonably inferred that the receptor of IL-39 is homo- or heterodimerized by IL-23R, IL-27R and gp130. Subsequent experiments proved that IL-39 signaling is carried out through the receptor complex of IL-23R and gp130. The two chains must be aggregated into a receptor complex and bind to IL-39 to activate STAT1 and STAT3 signaling molecules before transmitting signals.
IL-39 is a new member of the IL-12 family (composed of two subunits, IL-23p19 and EBI3). It shares the EBI3 subunit with IL-27 and IL-35. In human B lymphocytes infected with EB virus, EBI3 is high protein expression. At the same time, it was found that after lipopolysaccharides stimulated initial B cells in vitro, both IL-23p19 and EBI3 were expressed and the expression level was positively correlated with the length of lipopolysaccharide stimulation time. In lupus mice, GL7 + B cells and CD138 + plasma cells are highly activated and widely expressed. Activated GL7 + B cells and CD138 + plasma cells can promote high expression of IL-39 in mice, but GL7 + B cells produce IL The protein content of -39 is higher. Studies have shown that there are IL-23p19 and EBI3 mRNA expression in other immune cells such as dendritic cells and macrophages, and its mRNA expression level increases in the presence of IL-4. However, the study found that lipopolysaccharide has an inhibitory effect on the mRNA expression of IL-23p19 and EBI3 in dendritic cells and macrophages. These results indicate that there is a complex mechanism for the expression of IL-23p19 and EBI3 in lipopolysaccharide and dendritic cells, macrophages, and B cells, and further research is needed.
Fig 1. Mechanism of Signaling
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