A naturally occurring soluble form of Interleukin-27 receptor subunit, alpha(IL-27Ralpha) is termed soluble Interleukin-27 receptor subunit alpha (sIL-27Ralpha)and it is produced by human activated CD4(+) and CD8(+) T cells, B cells, myeloid cells, and various cell lines. Importantly, natural sIL-27Ralpha binds rIL-27(the heterodimer composed of the Interleukin-27 subunit alpha and Interleukin-27 subunit beta), inhibits IL-27 binding to its cell surface receptor and is a potent inhibitor of IL-27 signaling, as shown by its ability to specifically block IL-27-mediated STAT activation, at low molar excess over IL-27.
Interleukin-27 is a heterodimer composed of Interleukin-27 subunit alpha (IL27) and Epstein-Barr virus-induced gene 3 (EBI3). It binds to the Interleukin-27 heterodimeric receptor, which is composed of Interleukin-27 receptor subunit alpha (IL27RA, WSX-1) and Interleukin-6 receptor subunit beta (IL6ST, gp130). IL6ST is a signal transducing protein that is a component of several other cytokine receptors including the Interleukin-6 and Interleukin-11 receptors (Pflanz et al. 2004). In the absence of IL27RA, Interleukin-27 can bind to IL6ST but with low affinity (Jia et al. 2016).
Regulation: IL27RA can be cleaved releasing a soluble form (sIL27RA) that can bind to Interleukin-27 and antagonize Interleukin-27 binding to its heterodimer receptor (Dietrich et al. 2014).