IL-27 (mouse):Fc (LALA-PG)-KIH (human) (rec.)

Interleukin-12 (IL-12) family members are heterodimer glycoproteins, composed of two covalently linked subunits, alpha and beta chains. The alpha-subunit consists of IL-23p19, IL-27p28, and IL-12p35, and the beta-subunit includes IL-12p40 and Epstein-Barr virus-induced gene (Ebi3). IL-12 members bind to cognate heterodimeric receptor chains expressed on T cells. This family includes IL-12, IL-23, IL-27 and IL-35 and IL-39. IL-12 and IL-23 are predominantly proinflammatory cytokines that contribute key roles in the development of Th1 and Th17 cells, respectively. IL-27 has both pro- and anti-inflammatory properties and is a potent T cell immunomodulator. IL-35, a new member of this family, is a potent inhibitory cytokine produced by natural, thymus-derived regulatory T cell (nTreg) populations. IL-39, the newest member of IL-12 family, mediates the inflammatory response through the activation of STAT1/STAT3 signaling pathway. These IL-12 family members link innate immunity with the development of adaptive immunity and are also important for regulating T cell responses. IL-27 is composed of two subunits, IL-27p28 and Epstein-Barr virus-induced gene 3 (EBI3) signals via a heterodimeric receptor consisting of WSX-1 and glycoprotein (gp130), leading to activation of STAT 1 and 3. IL-27 is pro-inflammatory and promotes NK and T cell proliferation as well as the production of IFN-gamma. It is anti-inflammatory, inhibiting Th2 and Th17 cell activities and stimulating the production of IL-10 by T regulatory cells. IL-27 has potent antiviral activities against numerous viruses, by increasing the production of interferons (IFNs). Finally, IL-27 has antitumor activity as well as anti-angiogenic activity with activation of the production of anti-angiogenic chemokines. The protein IL-27 (mouse):Fc-KIH (human) (rec.) is produced by using two different vectors, one encoding for the IL-27A/p28:Fc Knobs sequence (synthesizing a protein of 62kDa) and one encoding for the IL27B/EBI3:Fc Holes sequence (synthesizing a protein of 60kDa). Both vectors transfected into CHO cells produce both Fc molecules (Knobs-into-Holes technology, J.B. Ridgway, et al., Protein Eng. 9, 617 (1996)) required for dimerization and for secretion of the final protein IL-27 (mouse): Fc (LALA-PG)-KIH (human) (rec.). The Fc contains the mutations LALA-PG that abolish the interaction between the Fc and FcgammaRs and therefore Fc undesirable effects.