IL-23 (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, 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 the 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. Interleukin-23 (IL-23) is composed of the IL-12 p40 chain covalently linked to p19, a chain related to the IL-12 p35 subunit. IL-23 signals through the IL-23 receptor complex, which is composed of the IL-12Rbeta1 chain and a gp130-like chain, IL-23R. Triggering of the IL-23 receptor complex leads to the activation of Tyk2, Jak2 and STAT1, 3 and 4. IL-23 induces IFN-gamma production, Th1 cell differentiation and activation of the antigen-presenting functions of dendritic cells. IL-23 induces autoimmune inflammation and thus may be responsible for autoimmune inflammatory diseases and important for tumorigenesis. The protein IL-23 (mouse):Fc (LALA-PG)-KIH (human) (rec.) is produced by using two different vectors, one encoding for the IL-23A/p19:Fc Knobs sequence (synthesizing a protein of 55kDa) and one encoding for the IL-12B/p40:Fc Holes sequence (synthesizing a protein of 75kDa). 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-23 (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.