Interleukin-35 heterodimer is formed by interleukin-12 alpha (IL12A or IL12p35) and Interleukin 27 subunit beta (EBI3). EBI3 monomer can be found at the endoplasmic reticulum and is not secreted since it remains associated to the protein calnexin (CANX). So is suggested EBI3 needs the association with another subunit to be released to the extracellular region (Devergne et al. 1996). Interleukin-35 affects and is specifically produced by regulatory T cells and regulatory B cells (Niedbala et al. 2007, Wang et al. 2014, Egwuagu et al. 2015, Fonseca-Camarillo et al. 2015). This interleukin is secreted and inhibits T cell proliferation (Collison et al. 2007).This reaction is a black box event because we know the Interleukin-35 heterodimeric protein is secreted but there is no reported evidence from which compartment and which mechanism is involved in the traslocation.